2. “Best Practices in making sure that
verification and validation
documentations are well understood”
Rommel B. Garcia
Consultant – Project Manager
3. • So you think you are intelligent and
you think you are right!
• Well, guess what, someone else
think that you are wrong!
“Mr.
O’Pinion”
4. A company in the past thru a recruiter
call me and wanted to engage.
The company’s name is:
“I will not tell”
They suffered several Major
Observation
5. 1. DESIGN VERIFICATION AND VALIDATION
• Failure to establish and maintain adequate procedures for verifying the
device design.
• Design verification shall confirm that the design output meets the design
input requirements, as required by 21 CFR 820.30
2. DESIGN HISTORY FILE
• Failure to establish and maintain a design history file for each type of
device, as required by 21 CFR 820.30
3. PROCESS VERIFICATION AND VALIDATION :
• Failure to ensure, when the results of a process cannot be fully verified by
subsequent inspection and test, that the process shall be validated with a
high degree of assurance and approved according to established
procedure, as required by 21 CFR 820.75 (a)
• Failure to establish procedures for monitoring and control of process
parameters for validated processes to ensure that the specified
requirements continue to be met, as required by 21 CFR 820.75(b).
6. A follow up inspection will be required to assure that correction and/or corrective actions
are adequate. Your firm should take prompt action to correct the violations addressed in this
letter.
• Failure to promptly correct these violations may result in regulatory action being initiated
by the FDA without further notice.
• These actions include, but are not limited to, seizure, injunction, and/or civil
money penalties.
• Also, federal agencies may be advised of the issuance of Warning Letters about devices
so that they may take this information into account when considering the
awarding of contracts.
• Additionally, premarket approval applications for the Class of devices to which the
Quality System regulation violations are reasonably related to will not be approved
until the violations have been corrected.
7. • An Accident?
• Paper Trail
• Not properly documented
• Missing documents
• No SOP
• Assessment
• Weak internal auditing practices
• Documents not defendable
8. • Identification of Gaps
• Standardization Practice
• Relearn Design Control
• The Risks
• What is CTQ and CQA
• Statistical Techniques
• Proper use of Lexicons
• Definitions V&V
• What is in V&V
• Understanding when to verify and when to
validated
• SOP
• Test Method Validation & MSA
• Documentations
• Stages
• DHF
• The Regulatory Body
9.
10. User
Needs
Concept Phase
- VOC information
- IDE
- Concept Study
- Clinical/Animal Studies
- VOC Design Review
- Intended Use
Design Input
DDP & Product
Requirements
Feasibility Definition Phase
- Design Development Plan
- Design Input Requirements
- Risk Management
- Design Reviews
Design Development Process
Design
Review
Design Output
Medical Device
Development Phase
- Design outputs created (Specifications /
Drawings / MSA / Test Methods Validation /
DVT (Design Verification Test), Supplier
Verification / Validation & Approval / etc.)
- Design Reviews
Device Qualification Phase
- Packaging / Sterility Ver. & Val.
- Device / Design Validation
- Process Validation
- DMR/DHR
- Design Transfer / Review
- Review and update Risks
- Shelf Life Verification/Study
- Design Freeze
- R/A Submissions / Approval
Product Closure Product Launch
Product Launch
- Post-Market Surveillance
- Production Review
- Return Analysis, RMR/RCA
as Needed
- Review and update RMF
- Release product for sale ECO
- Equipment / System Validation
END of Life - Decommissioning
Device Validation
D.V.T.
11. • Why are we talking about Risk….
• It is part of the “QMS”
• ISO14971
• Is the “How to identify the hazard associated with the device”
• Estimate the risk associated with the hazard
• Risk Management Processes Elements
• Risk Identification / Analysis
• Risk Evaluation
• Risk Control
• Risk Assessment
12. • CTQ - are key measurable characteristics of a component or process whose performance
standards or specification limits that must be met in order to satisfy the customer requirement
• CQA - a physical, chemical, biological or microbiological property or characteristic that shall
be within an appropriate limit, range, or distribution in order to ensure the desired product
quality.
• Therefore:
• The purpose of CTQ is to convert user needs to a measurable requirement (Specification)
• While the purpose of CQA is to convert the CTQ further for business to implement in manufacturing.
SO:
CTQ is in the Design Control stage and the CQA is in the Manufacturing stage.
Ref:
Early,J.F. and O.Coletti. Section 3: “The Quality Planning Process. ”Juran’s Quality Handbook. 5thEd. 1999
13. • When do we use the following words:
• Shall
• Should
• May
• Quiz……
• Which of the statements is correct:
1. We may follow all the regulation in 21CFR 820
when we produce or manufacture medical
device.
2. We shall follow our company’s Quality System
Regulation.
3. We should invest in our company’s 401K
14. • Verification is looking for an objective evidence that the
“product” (which is a widget) is being produced correctly”.
• Validation is looking for objective evidence that the “widget is
the correct product”
15. • Activities in:
• Verification
• Worst Case Analysis
• Thermal Analysis
• Fault Tree Analysis
• Package Integrity Analysis
• Biocompatibility Analysis
• Bioburden Analysis
• Leveraging
• Validation
• Types
• Validation of Process
• Validation of Test Methods
• Validation of Equipment
• Documents
• Validation Planning VMP
• Validation Protocol
• Validation Report
Documentation
Repository
16. • An Example:
• Adhesive Material
• When is verification
applicable and when is
validation applicable…
17. • Subpart “O” or 820.250
• Requires manufacturers to establish and maintain procedures for
identifying valid statistical techniques
• Sampling Plans
• Attribute: N=ln(1-CL)/lnR
• Variable: n=3/P
• Capability Analysis
• Statistical Analysis
• others
18. “Failure to document how to review sampling methods for adequacy for their
intended use, as required by 21 CFR 820.250(b). “
• Do what you say, Say what you do:
• One thing leads to another….
• Why do we need an SOP?
• The Purpose
• The Command
• How do we make it Compliant?
• Compliance/Training Team
• The Task
• Review
• Distribution
• Training
• Metrics
19. • Definitions
• Difference between TVM and MSA
• Not much
• Deliverables
• Accuracy
• Precision
• Repeatability
• Reproducibility
• Specificity
• Sensitivity
• Linearity
• But why do we do it?
20. • Contents of Design History File
• The contents will probably vary from class to class, company to company and
from industry to industry
• In general, the contents should be:
• Design Development Plans
• Design Input Documentations
• Design Risk Documentation and Pointers (RMF)
• Design Output Documentations
• Design Reviews Documentations
• Design Verification Documentations
• Design Validation Documentations (including Shelf Life)
• Design Trace Matrices Documentations
• Design Transfer Documentation
• Change Control Documentations
21. • An FDA Audit probability
• What will they look for…..
• Design Control SOP
• Did you properly audit your documents against the QSR
• Did I we do a good sample
• Change Controls
• Do we have any changes
• What is common sense in changes
• What is LESLI (LESsons Learned Index)
• Why
• Sampling Metrics
22. • What do they normally do?
• Sequence
• Why
• Quality System
• MDR / Complaints / Adverse Events
• CAPA
• Trending
• QSIT
• Probability High
• DHF
• Documents
• Trace Matrices?
• Questions and documentations
• Are you ready?
• These are all valid concerns and expectation from FDA
23. • When put all of the items together:
• Test Methodologies – how do we standardized the
configuration of documenting them
• We have discussed the Test Method Validation and
MSA
• What are the critical requirements that should be met
• We have also discussed the background statistics
• What does the regulatory body expects from
Verification and Validation records
• We have discussed an experience that I had when
one of the company that got a warning letter and
the activities that we did to remediate.
• In the last slide, I have given you example of what
FDA will possibly ask so take note
• Validation lifecycle documentation multiphasic process
• We have discussed the different elements of
validation with respect to Design Control and the
phases involved.
24. PLEASE BE KIND TO ANIMALS LIKE ME
For more questions… please send me email me:
melmaan2010@gmail.com
