Validation Medical Device

Roadmap for Medical Device
Process Validation
Jacalyn L. Schroeder
Statistician, Validation/Quality
Engineering Specialist
Medical Products
2
Jackie Schroeder
Presenter
 B.S. in Chemical Engineering
 M.S. in Applied Statistics
 23 Years at 3M
 2 Years at Dow Chemical
 Medical Devices, Drug Combo Products
 Mfg Engineer, Product Service Engineer, Supervisor,
Validation Engineer, Quality Engineer
 Validation Engineer – 8 Years
 Global Presenter on Process Validation
 Quality Engineering Specialist
J.L. Schroeder , 3M, April 2016
Process Validation Experience
Participant Input
 Expert ‐ Conducted many Process
Validations
 Experienced ‐ Conducted a few Process
Validations
 Rookie – Have read Process Validation
Guidance
 Curious ‐ Heard of Process Validation
Agenda
 What is Process Validation?
 Why do Process Validation?
 When do Process Validation?
 Stages of Process Validation
 Elements of Process Validation
 “Real Life” Process Validation Case Study
WHAT is
Process Validation?
 § 820.3 (z)(1): “Establishing by objective
evidence that a process consistently produces
a result or product meeting its predetermined
specifications.”
 FDA Guidance Document:
• “Collection and evaluation of data, from the
process design stage through commercial
production, which establishes scientific evidence
that a process is capable of consistently
delivering quality product.”
WHY do Process Validation:
Regulations
• Medical Device
– Quality System Regulation: (QSR) 21 CFR 820
– Medical Device Quality Systems: ISO 13485
– Medical Devices – Risk Management: ISO 14971
• Pharmaceutical
– Current Good Manufacturing Practice: 21 CFR 210 & 211
– Pharmaceutical Development: ICH Q8
– Risk Management: ICH Q9
– Pharmaceutical Quality Systems: ICH Q10
• Combination Products
– cGMP for Combination Products: 21 CFR 4
WHY do Process Validation:
Regulations
• § 820.75 (a): “Where the results of a process cannot
be fully verified by subsequent inspection and test,
the process shall be validated with a high degree of
assurance and approved according to established
procedures.”
• § 211.110(a): “Control procedures shall be
established to monitor the output and to validate
the performance of those manufacturing processes
that may be responsible for causing variability in the
characteristics of in‐process material and the drug
product.” J.L. Schroeder , 3M, April 2016 10
The following RISK BASED model may be useful in
determining whether or not a process should be validated:
A
B C
Is P ro c e s s
I s V e r if ic a t io n V e r if y &
O u tp u t Yes
Y e s
S u ff ic ie n t & Yes
Y e s
C o n tro l th e
C o s t E ffe c tiv e P ro c e s s
V e r if ia b le
N o N o
•FDA: “FDA encourages
No the use of modern
pharmaceutical
development concepts,
quality risk
management, and
Validate Redesign
quality systems at all
stages of the
D
R e d
E
e s ig n manufacturing process
V a lid a te P ro
a n
d
d
u c t
/o r
lifecycle.”
P ro c e s s
GHTF/SG3/N99‐10:2004 (Edition 2)
Lifecycle Approach
FDA: “Guidance aligns process validation activities with a
product lifecycle concept and with existing FDA guidance
[documents]…FDA encourages the use of modern
pharmaceutical development concepts, quality risk
management, and quality systems at all stages of the
manufacturing process lifecycle.”
Development
(Product &
Process)
Control of Qualification
Process of Process
12
WHEN do Process Validation?
 New Products/Formulations into facility
 Desire to scale‐up process outside the previous validated range
 Existing products manufactured in a new facility or on new
equipment
 When change is made to the manufacturing or processing methods
 Change to existing formulation
 Change made to raw material that could result in a change in the
material properties/characteristics or grade which could
subsequently affect the product quality or process performance
 When new equipment or utilities that are not “like for like” are
introduced
 When significant changes are made to the processing conditions or
environment
 When a significant shift in process or a change in the process
capability is observed
 When a change is made to a primary packaging, e.g. closure system
Validation Stages –
A Lifecycle Approach
 Stage 1 – Process Design: The commercial
manufacturing process is defined during this stage
based on knowledge gained through development
and scale‐up activities.
 Stage 2 – Process Qualification: During this stage,
the process design is evaluated to determine if the
process is capable of reproducible commercial
manufacturing.
 Stage 3 – Continued Process Verification: Ongoing
assurance is gained during routine production that
the process remains in a state of control.
J.L. Schroeder , 3M, April 2016 14
HOW do we Validate?
Product Design
Publish Product Validation Defined
Plan
Publish Equipment System

Specifications
Qualify Equipment
Publish Equipment Design & Operation
Installation/Operation
Qualification (IOQ) Protocol
Equipment Design
Defined
Complete Product & Process
Understanding (PPU) Work Qualify Process
Performance
Publish IOQ Report
Initial Process
Capability Understood
Publish Performance
Qualification (PQ) Protocol(s)
Execute PQ Protocol(s) then

Publish PQ Report(s)
Continuously monitor
to ensure validated
BEGIN PRODUCTION FOR SALE
state
Elements of Process Validation
Perform PQ
Validation
per Protocol
Equipment Monitor
Risk Qualification PPU PQ Transfer to
PQ Report and
Assessment Studies Protocol Production
IQ/OQ Review
Perform PQ
Validation
per Protocol
Stage 2
Equipment Monitor
PQ Report and
IQ/OQ Review
Stage3
Validation Responsibilities
 Manufacturing Engineer: Complete PPU work to establish critical
process parameters and establish process limits for validation.
 Validation Engineer or Manufacturing Engineer: Co-write validation

documents and assist with validation work as needed. Work with
technology personnel to setup applicable PMs.
 Product Service (Laboratory) Engineer: Approve validation documents

as required.
 Quality Assurance: Approve validation and approve validation

performance levels (for sample size and acceptance criteria).
 Trained Production Personnel: Run and sample product for PPU work
and validation.
 Validation Steering Committee: Review all validation documents and

advise on validation and PPU issues.
Medical Device Process Validation
Case Study
It is desired to change the adhesive coat weight for an
existing medical tape. Is Validation Required?
Medical Device Process Steps
Make or Adhesive
purchase Coating/ Slitting Converting Packaging
Backing Drying
Assess the Risk of the Change
Perform PQ
Validation
per Protocol
Equipment Monitor
PQ Report and
IQ/OQ Review
Risk Management
Assess impact of risk, per device requirements, in the

areas of safety, efficacy, regulatory, appearance, and dollar
loss.
Risk Management
Once the risk level is defined, determine if validation is

required. Use the highest rated risk for each particular
device requirement to determine if validation is
required.
Document validation requirements in Validation Plan.
Validation Plan – Risk Assessment
Case Study
Document Risk Assessment
Based upon
information in
Design
Documentation
Approved by
Laboratory,
Quality Assurance
and
Regulatory
Representatives.
23
Case Study
Per Risk Assessment – Validate Adhesive Coat
Weight
Perform PQ
Validation
per Protocol
Equipment Monitor
PQ Report and
IQ/OQ Review
IQ and OQ Best Practices
 Combine IQ/OQ into single template ‐ ‐ ‐ IOQ
 Use approved validation templates, whenever
possible
 Use certified instruments for testing
 Get buy‐in on Critical Process Parameters (CPPs)
 PFMEA
 Document product can be made at extremes (for
sterile seals, capability at extremes)
 Equipment calibrations over range of use
 CPPs (KPPC) must be recorded
IQ and OQ Main Components
Case Study
DESCRIPTION ACTUAL
Background (Document background of equipment or process This IOQ is being prompted by a change to the
and what is prompting IOQ) adhesive coat weight specification for an existing
medical tape.
Intent (Document either validation or qualification)
* Intent: Validation (Prerequisite to
Validation: Performance Qualification (PQ))
Note: There are two options. Select only one option.
* Prerequisite to Performance Qualification (PQ)
* IOQ only required to "validate for intended use."
Qualification: IOQ used to qualify or verify change.
Qualified Characteristics
* Validation Plan: Validation Plan 1
(Document Validation Plan Name and Key Product * KPPC: Product adheres satisfactorily.
Performance Characteristics (KPPC) from Validation Plan, if * Qualified Characteristic: Adhesive Coating
applicable. Otherwise, document N/A. Document Weight
characteristics to be qualified per this IOQ.)
Case Study
EQUIPMENT QUALIFIED CHARACTERISTIC(S)
Coater1 Coating Weight
Case Study
Operating Range
to Qualify
Equipment
PPU: Experiment
documenting
Experiment 456
Process Standard
operating range
Case Study
Case Study
• IQ – listing of critical equipment, hardware,
software, utilities, PM’s and documentation
Case Study
• OQ – operational confirmation of equipment,
software management plan
Item Expected Actual How Verified Verified By/

Date
Coater Line Ensure that Linespeed was within 5% of setpoint. 4 Speeds checked. Using a John Doe/1‐21‐
Speed linespeed is Speeds checked were xxxx, yyyyy, zzzzz, aaaaa. calibrated 16
within 5% of device
setpoint. Please
check a
minimum of 4
actual
linespeeds over
the range of use
per PM:
LINESPEED J.L. Schroeder , 3M, April 2016 31
Case Study
Item Expected Actual How Verified Verified By/Date

SOFTWARE PROGRAM
Document how the Changes saved on system at As Expected Verify with John Doe/1‐21‐16
EQUIPMENT program is line are time stamped to system
backed up. Document if the indicate next version. administrator
program is saved with an
independent time‐stamp or Backups saved at location
version to record actions xxx have both time stamp
that create, modify, or along with a version change.
delete
electronic records.
Item Expected Actual How Verified Verified By/Date

Linespeed Process Set‐ Operator cannot run Operator cannot run Visual/Tested John Doe/1‐21‐16
point Deviation faster than the standard faster than the standard
maximum. maximum.
Perform PQ
Validation
per Protocol
Equipment Monitor
PQ Report and
IQ/OQ Review
Product and Process Understanding (PPU)
• Can be one experiment or several
• Pre‐requisite to validation activities
• Information gathering and critical process parameter
identification
• Identifies “Process Standard” Operating range –
Document in OQ
• Sterile Seals: Capable process demonstrated at
extremes
• Obtain predicted process Ppk for validated
characteristics;
• Use to determine sample size and acceptance criteria for
validation.
• Obtain verification data for verified characteristics
Estimated Process Capability
V o ic e o f C u s to m e r N ea rest Spec  A ve
Pˆ p k  
V o ic e o f P r o c e s s 3
Numerator
LSL USL
Denominator
Target
To be validated with PQ:
• Adhesive Coat Weight Perform PQ
Validation
per Protocol
Equipment Monitor
PQ Report and
IQ/OQ Review
Performance Qualification –
Important Learning for PQ
 Run at nominal conditions to represent future production.
 Form product families and validate worst case product(s).
 Validation is confirmation not experimentation.
 PPU work is very important to ensure that validation does not
fail…no surprises.
 Should not consider validation if PPU estimated process
capability is not greater than or equal to 1.0 (Ppk>1.0)
 Validation not a one person effort; Team effort.
 Steering Committee Important for Consistency. Steering team
to include members from manufacturing and quality
management.
 Acceptable measurement system based off Gage R & R
Performance Qualification
Important Learning
• Need Representative Sample: Stratified and periodic
sampling is desired over complete random sampling.
Keep samples in time order for analysis.
• Combine documentation, where applicable (i.e. IOQ)
• Reasons Problems Aren’t Found During Validation:
– Missing requirement or failure mode.
• Could perform FMEA to help prevent.
– Inadequate sample size.
– Not representative sample.
Performance Qualification –
Important Learning
 Have quality approve projects (manage change) for manufacturing
changes.
 Have a good process to understand critical operating parameters
controlling critical quality attributes.
 Use valid statistical rationale to determine sample size.
 Use statistically based sampling plans.
 Upon passing plan, make confidence statement based on risk.
 Use plan with ability to perform attribute validation, if required.
 Good resource is www.variation.com (Taylor Enterprises, Inc.)
 Reference Books located on website.
 PER FDA Guidance: Homogeneity within a batch and consistency between
batches are goals of process validation activities.
 Run multiple batches and change most variable component between batches
(i.e. raw material, setups)
Steps to Choose Statistical
Based Sampling Plan for Validation
Step 1a: Select Performance Level
 Performance Level should be
selected based on risk
Resource: Dr. Wayne Taylor
Validation Sampling Plan Class
‐ 2008
Step 1a: Performance Levels
[LTPDβ] for PQ
• Commonly used in pharmaceutical and
medical device industries for disposables
are:
– For Defect (Health and Safety)
0.065%, 0.1%
– For Defects (Functional)
0.25%, 0.4%, 0.65%, 1.0%
– For Defects (Cosmetic)
2.5%, 4.0%
Resource: Dr. Wayne Taylor J.L. Schroeder , 3M, April 2016
‐ 2008
Step 1a: Performance Levels
[LTPDβ] for PQ
• Commonly used in medical device industry for
hardware and very expensive devices are:
– For Critical Defect (Health and Safety)
0.1% (99.9% reliability), 0.3% (99.7% reliability),
1% (99% reliability)
– For Major Defects (Functional)
1% (99% reliability), 3% (97% reliability), 5% (95%
reliability)
– For Minor Defects (Cosmetic)
5.0% (95% reliability), 10% (90% reliability)
Validation Sampling Plan Class J.L. Schroeder , 3M, April 2016
‐ 2008
Step 1b:
Determine Confidence Level (1‐β)
to make CONFIDENCE STATEMENT
Confidence Level Recommendations:
Recommend using Consumer Risk (β) of
 β=5% or 10%
Equates to (1‐β)
95% or 90% Confidence Level
Step 2: Determine BEST Sampling Plan
based on ESTIMATED AQL
For Variables Data: Use estimated Ppk to
estimate AQL
For Attribute Data: An estimated AQL
may be determined from history or
estimated from experimental runs
Step 2: Determine BEST Sampling
Plan based on ESTIMATED AQL
 Choose between Attribute and Variables
Data Plans
 Use Validation Sampling Plan Tables
(www.variation.com)
 Select BEST Sampling Plan
– Compare samples sizes and AQLs to determine
best choice at a specified performance level
Validation Sampling Plan Class J.L. Schroeder , 3M, April 2016
‐ 2008
Step 2: Select BEST Sampling Plan
• Choose Attribute or Variables Plans
• Use tables in Process Validation Sampling Plans
SOP
• LTPD:
– 20%, 10%, 6.5%, 5%, 4%, 3%, 2.5%, 1.5%, 1%, 0.65%, 0.4%,
0.3%, 0.25%, 0.15%, 0.1%, 0.065%
• Tables:
– Attribute 90% Confidence
– Attribute 95% Confidence
– Variables 1‐Sided 95% Confidence
– Variables 2‐Sided 95% Confidence
Validation Sampling Plan Class J.L. Schroeder , 3M, April 2016 47
‐ 2008
Validation
per Protocol
Equipment Monitor
PQ Report and
IQ/OQ Review
PQ Main Components
Case Study
1. Scope
An existing product requires a new coat weight range. This requires coat weight
validation per Validation Plan1.
2. Purpose
2.1 Operating Process Limits
The purpose of this validation protocol is to show with a high degree of assurance that
products coated on adhesive Coater1 can consistently be manufactured to meet
product coating weight specifications:
* Coating Weight Range: XXX - YYY
The critical process controls to achieve coating weight on Coater1 are:
* Process Control 1
* Process Control 2
The process limits for Process Control 1 and Process Control 2 were defined by PPU
work completed under Experiment456.
PQ Main Components
Case Study
3. Methodology
3.1. PPU (Product and Process Understanding Work)
Experiment456 estimated the adhesive coating weight process capability Ppk at
2.15. This coating weight capability was determined by adhesive coating at
nominal conditions. The predicted Ppk value was acquired by testing 3 locations
crossweb and 6 locations downweb. All data passed the appropriate data
distribution tests.
The process extremes were confirmed with Experiment456.
3.2. Validation PPE and Qualified Equipment

This validation will be run under Experiment789. Coater1 was qualified per IOQ-
503.
3.3. Products Covered Under Validation and Worst Case Products

There is only one product produced at this coat weight range; therefore, Product
1 will be represented by this validation.
PQ Main Components
Case Study
3.4. Validation Performance Level and Confidence Level
A performance level and a 95% confidence level will be used to
determine if this validation passes. Per review with management via the
Brookings Process Validation Steering Committee, this protocol will
require a performance level (RQL or LTPD) of 1% for adhesive coating
weight. Performance Level and Confidence Level determines
validation sample size and acceptance criteria
3.5. Validation Lot Specifics
For validation, three total lots will be coated, comprised of at least 2 lots
of adhesive during one production run and a separate production run for
the third lot. The machine will also be shutdown between lots.
Each validation lot will be a target of approximately 2000 lnyds each.

Production lengths of 2000 lnyds, per validation lot, is representative of
expected production run lengths.
PQ Main Components
Case Study
3.6. Target Sample Size Requirements
The 95% Confidence Sampling Plan Tables, as documented in SOP123,
will be used for validation. These tables were derived from an Operating
Characteristic or OC curve based on a certain AQL (Acceptable Quality
Level) and LTPD (Lot Tolerance Percent Defective).
Section 3.1 above indicates that the "estimated" coat weight process
Ppk is 2.15. Based on a Ppk of 2.15 the target number of samples is
n = 15 samples per lot and will be collected cross and downweb for
each lot.
3.7 Validation Sample Size Requirements and Acceptance Criteria

Samples will be gathered from a full web sample at startup and
throughout the validation run. These full web samples will then be
tested crossweb at 3 locations crossweb; left, center and right.
SOP123
L TP D = 1 %
A tt ri b u te P la n s w i th 9 0 % C o n f i d e n c e A tt ri b u t e P l a n s w ith 9 5 % C o n f id e n c e
T yp e P ar am eter s AQL L T P D 0 .1 T y pe P a ra m e t e rs AQL L T P D 0 .0 5
S in g le n=2 30, a=0 0 .0 2 % 1% S ingle n =30 0, a= 0 0.02% 1%
D o uble n 1 = 2 5 0 , a 1 = 0 , r1 = 2 , n 2 = 4 0 0 , a 2 = 2 0 .1 1 % 1% D o u b le n 1= 325, a1= 0, r1 =2, n2= 400 , a2= 2 0.09% 1%
V a r ia b l e s – 1 -s id e d – 9 5 % C o n fid e n c e V a ria b l e s – 2 -s i d e d – 9 5 % C o n fi d e n c e
P a r a m e t e rs AQL L T P D 0 .0 5 Par am eter s AQL L T P D 0 .0 5
n=1 5, P pk =1 . 17 0 .0 0 0 1 7 % ( P p k = 1 .5 5 ) 1 % ( P p k = 0 .7 8 ) n = 1 5 , P p k = 1 .1 7 , P p = 1 . 1 7 0 .0 0 0 1 6 % ( P p k = 1 .5 5 ) 1 % ( P p k = 0 .7 8 )
n=2 0, P pk =1 . 10 0 . 0 0 1 2 % ( P p k = 1 .4 1 ) 1 % ( P p k = 0 .7 8 ) n = 2 0 , P p k = 1 .1 1 , P p = 1 . 1 3 0 .0 0 1 % (P p k = 1 .4 2 ) 1 % ( P p k = 0 .7 8 )
n=3 0, P pk =1 . 0 2 0 .0 0 8 % (P p k = 1 .2 6 ) 1 % ( P p k = 0 .7 8 ) n = 3 0 , P p k = 1 .0 3 , P p = 1 . 0 7 0 .0 0 7 % (P p k = 1 .2 7 ) 1 % ( P p k = 0 .7 8 )
n=4 0, P pk =0 . 98 0 .0 2 % ( P p k = 1 . 1 8 ) 1 % ( P p k = 0 .7 8 ) n = 4 0 , P p k = 0 .9 9 , P p = 1 . 0 4 0 .0 1 8 % (P p k = 1 .1 9 ) 1 % ( P p k = 0 .7 8 )
n=8 0, P pk =0 . 9 1 0 .0 9 % ( P p k = 1 . 0 4 ) 1 % ( P p k = 0 .7 8 ) n = 8 0 , P p k = 0 .9 2 , P p = 0 . 9 9 0 .0 8 % ( P p k = 1 . 0 5 ) 1 % ( P p k = 0 .7 8 )
n = 1 0 0 , P p k = 0 .8 9 0 .1 3 % ( P p k = 1 . 0 1 ) 1 % ( P p k = 0 .7 8 ) n = 1 0 0 , P p k = 0 . 9 0 , P p = 0 .9 7 0 .1 1 % ( P p k = 1 . 0 2 ) 1 % ( P p k = 0 .7 8 )
Sample Size & Estimated Ppk
Ppk To Pass
Tables Developed from Validated “Sampling Plan Analyzer” – Version 2.0
Copyright 2001 Taylor Enterprises Inc.
PQ Main Components
Case Study
3.7 Validation Sample Size Requirements and Acceptance Criteria
Samples will be gathered from a full web sample at startup and throughout the validation
run. These full web samples will then be tested crossweb at 3 locations crossweb; left,
center and right.
See the table below for testing position, target sample size and corresponding pass/fail
criteria. It should be noted that statistically there is no maximum sample size for sampling
plans located in SOP123. Therefore, the author must simply choose a sample size that is
both cost effective and provides a reasonable estimate of process variability (i.e. more
samples gives a better estimate of the true process variability). If desired, additional
samples taken from the same lot and during the same time period, may be tested and
compared to the appropriate acceptance criteria in SOP123. If fewer samples are taken,
justification will be recorded in the report and the corresponding acceptance Ppk will be
determined per the validation sampling plan "Variables-2-sided and 95% Confidence for
1% LTPD" found in SOP123.
TABLE 3.7
Process Name Test Specification Acceptance Criteria
Coater1 Coat Weight TS Coat Specification A Target n = 15 Total
*Min Ppk to pass at
J.L. Schroeder , 3M, April 2016 N = 15: 1.17 54
SOP123
L TP D = 1 %
A tt ri b u te P la n s w i th 9 0 % C o n f i d e n c e A tt ri b u t e P l a n s w ith 9 5 % C o n f id e n c e
T yp e P ar am eter s AQL L T P D 0 .1 T y pe P a ra m e t e rs AQL L T P D 0 .0 5
V a r ia b l e s – 1 -s id e d – 9 5 % C o n fid e n c e V a ria b l e s – 2 -s i d e d – 9 5 % C o n fi d e n c e
P a r a m e t e rs AQL L T P D 0 .0 5 Par am eter s AQL L T P D 0 .0 5
n=1 5, P pk =1 . 17 0 .0 0 0 1 7 % ( P p k = 1 .5 5 ) 1 % ( P p k = 0 .7 8 ) n = 1 5 , P p k = 1 .1 7 , P p = 1 . 1 7 0 .0 0 0 1 6 % ( P p k = 1 .5 5 ) 1 % ( P p k = 0 .7 8 )
n=2 0, P pk =1 . 10 0 . 0 0 1 2 % ( P p k = 1 .4 1 ) 1 % ( P p k = 0 .7 8 ) n = 2 0 , P p k = 1 .1 1 , P p = 1 . 1 3 0 .0 0 1 % (P p k = 1 .4 2 ) 1 % ( P p k = 0 .7 8 )
n=3 0, P pk =1 . 0 2 0 .0 0 8 % (P p k = 1 .2 6 ) 1 % ( P p k = 0 .7 8 ) n = 3 0 , P p k = 1 .0 3 , P p = 1 . 0 7 0 .0 0 7 % (P p k = 1 .2 7 ) 1 % ( P p k = 0 .7 8 )
n=8 0, P pk =0 . 9 1 0 .0 9 % ( P p k = 1 . 0 4 ) 1 % ( P p k = 0 .7 8 ) n = 8 0 , P p k = 0 .9 2 , P p = 0 . 9 9 0 .0 8 % ( P p k = 1 . 0 5 ) 1 % ( P p k = 0 .7 8 )
n = 1 0 0 , P p k = 0 .8 9 0 .1 3 % ( P p k = 1 . 0 1 ) 1 % ( P p k = 0 .7 8 ) n = 1 0 0 , P p k = 0 . 9 0 , P p = 0 .9 7 0 .1 1 % ( P p k = 1 . 0 2 ) 1 % ( P p k = 0 .7 8 )
Tables Developed from Validated “Sampling Plan Analyzer” – Version 2.0
Copyright 2001 Taylor Enterprises Inc.
PQ Main Components
Case Study
3.8 Confidence Statement For Passing Validation
Per 95% Confidence Sampling Plan for LTPD = 1% the adhesive
coating process will pass validation if the acceptance criteria
documented in Section 3.7 is met. Therefore, if this validation
passes we can say with 95% confidence that the process for
controlling adhesive coating weight is less than 1% defective.
Confidence Statements
• Conclusion when pass a sampling plan
• Sampling plans are designed to demonstrate
that the product tested meets a specified
performance level (LTPDβ)with certain
confidence (typically 1 – β or 95%)
• Passing the plan n=300, a=0 allows one to
state: “With 95% confidence the defect level is
below 1% defective.”
‐ 2008
PQ Report Main Components
Case Study
1. Scope
An existing product requires a new coat weight specification. This
requires coat weight validation per Validation Plan1.
2. Conclusions
Validated: Yes
Per the acceptance criteria set forth in validation protocol VP‐503 this
validation passes. Therefore, we can say with 95% confidence that the
process for controlling adhesive coating weight is less than 1% defective.
Case Study
Acceptance Criteria:
The following validation sampling plans located in SOP123 were used. See
acceptance criteria, tests, sample size, and specifications:
Coating Weight: Per "95% Confidence Sampling Plan for LTPD = 1.0% ‐ 2
sided"
Process Name Test Specification Acceptance Criteria

Coater1 Coat Weight TS Coat Specification A Target n = 15 Total
*Min Ppk to pass at
N = 15: 1.17
Case Study
3. Summary of Study
The Experiment was executed on December 8th, 2015
with the validation lots produced under reports
R092088 and R092110.
According to the validation protocol three total lots
were to be coated, comprising of at least 2 lots of
adhesive during one production run and a separate
production run for the third lot. A total of 15 coat
weight tests were performed on each lot as specified in
Table 3.7 of the validation protocol.
Case Study
4. Detailed Results
4.1 Data Analysis
Lot 1 Adhesive Coating Weight:
• Assess control
• Assess normality
• Assess process
capability
• If data not normal,
transpose data or find
best non‐normal
distribution
Case Study
• Assess control
• Assess normality
• Assess process
capability
• If data not normal,
transpose data or find
best non‐normal
distribution
Validation
per Protocol
Equipment Monitor
PQ Report and
IQ/OQ Review
Validation
per Protocol
Equipment Monitor
PQ Report and
IQ/OQ Review
Stage 3 – Monitor and Review
• Objective
– Ensure process remains in validated state and state of
control during commercial manufacture. A system or
systems for detecting unplanned departures from the
process as designed is essential to accomplish this goal.
• FDA Guidance Recommendations:
– Data should be statistically trended.
– Continued monitoring and sampling of process
parameters and quality attributes at the level established
during process qualification stage until sufficient data are
available to generate significant variability estimates.
Important Learning
• Re‐validate as part of routine production
whenever possible.
– Use risk management and change control to determine when re‐
validation required.
• Use statistical process control charts (SPC)
charts when it makes sense.
• Get management support of continuous
process verification activities.
• Develop and maintain (Engineers and
Operators) SPC training program to establish
and maintain SPC culture.
Annual Ppk & Risk Management Review
Questions?
Contact Information
Jacalyn L. Schroeder – 3M Company
Title: Quality Engineering Specialist; MS
Applied Statistics 2013
E‐mail: jlschroeder2@mmm.com
Work Phone: 605‐696‐1355
References
1. Dr. Wayne A. Taylor, “Guide to Acceptance
Sampling”, version 1, www.variation.com, Taylor
Enterprises,Inc. Note: Version 2 of new book
2013‐2014.
2. GHTF/SG3/N99‐10:2004 (Edition 2) , “Quality
Management Systems ‐ Process Validation
Guidance”, January 2004
3. Validation Sampling Plan Course, Wayne Taylor,
March 2008
4. Vladimir, Veselov, Helen Roytman, Lori
Alquier, “Medical Device Regulations for
Process Validation: Review of FDA, GHTF,
and GAMP Requirements”, Journal of
Validation Technology, spring 2012
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Validation Medical Device

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Validation Medical Device

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Roadmap for Medical Device

Publish Equipment System

Publish IOQ Report

Execute PQ Protocol(s) then

 Validation Engineer or Manufacturing Engineer: Co-write validation

 Product Service (Laboratory) Engineer: Approve validation documents

 Quality Assurance: Approve validation and approve validation

 Validation Steering Committee: Review all validation documents and

Assess impact of risk, per device requirements, in the

Once the risk level is defined, determine if validation is

Item Expected Actual How Verified Verified By/

Item Expected Actual How Verified Verified By/Date

Item Expected Actual How Verified Verified By/Date

* Coating Weight Range: XXX - YYY

The critical process controls to achieve coating weight on Coater1 are:

The process extremes were confirmed with Experiment456.

3.2. Validation PPE and Qualified Equipment

3.3. Products Covered Under Validation and Worst Case Products

Each validation lot will be a target of approximately 2000 lnyds each.

3.7 Validation Sample Size Requirements and Acceptance Criteria

T yp e P ar am eter s AQL L T P D 0 .1 T y pe P a ra m e t e rs AQL L T P D 0 .0 5

S in g le n=2 30, a=0 0 .0 2 % 1% S ingle n =30 0, a= 0 0.02% 1%

S in g le n=3 90, a=1 0 .0 9 % 1% S ingle n =47 0, a= 1 0.08% 1%

D o uble n 1 = 2 5 0 , a 1 = 0 , r1 = 2 , n 2 = 4 0 0 , a 2 = 2 0 .1 1 % 1% D o u b le n 1= 325, a1= 0, r1 =2, n2= 400 , a2= 2 0.09% 1%

S in g le n=5 30, a=2 0 .1 5 % 1% S ingle n =63 0, a= 2 0.13% 1%

D o uble n 1 = 2 5 0 , a 1 = 0 , r1 = 3 , n 2 = 5 6 0 , a 2 = 3 0 .1 8 % 1% D o u b le n 1= 325, a1= 0, r1 =3, n2= 580 , a2= 3 0.15% 1%

S in g le n=6 70, a=3 0 .2 0 % 1% S ingle n =77 0, a= 3 0.18% 1%

D o uble n 1 = 2 5 0 , a 1 = 0 , r1 = 3 , n 2 = 7 2 0 , a 2 = 4 0 .2 1 % 1% D o u b le n 1= 325, a1= 0, r1 =3, n2= 720 , a2= 4 0.18% 1%

T yp e P ar am eter s AQL L T P D 0 .1 T y pe P a ra m e t e rs AQL L T P D 0 .0 5

S in g le n=2 30, a=0 0 .0 2 % 1% S ingle n =30 0, a= 0 0.02% 1%

S in g le n=3 90, a=1 0 .0 9 % 1% S ingle n =47 0, a= 1 0.08% 1%

D o uble n 1 = 2 5 0 , a 1 = 0 , r1 = 2 , n 2 = 4 0 0 , a 2 = 2 0 .1 1 % 1% D o u b le n 1= 325, a1= 0, r1 =2, n2= 400 , a2= 2 0.09% 1%

S in g le n=5 30, a=2 0 .1 5 % 1% S ingle n =63 0, a= 2 0.13% 1%

D o uble n 1 = 2 5 0 , a 1 = 0 , r1 = 3 , n 2 = 5 6 0 , a 2 = 3 0 .1 8 % 1% D o u b le n 1= 325, a1= 0, r1 =3, n2= 580 , a2= 3 0.15% 1%

S in g le n=6 70, a=3 0 .2 0 % 1% S ingle n =77 0, a= 3 0.18% 1%

D o uble n 1 = 2 5 0 , a 1 = 0 , r1 = 3 , n 2 = 7 2 0 , a 2 = 4 0 .2 1 % 1% D o u b le n 1= 325, a1= 0, r1 =3, n2= 720 , a2= 4 0.18% 1%

Process Name Test Specification Acceptance Criteria

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