Validation
Acceptance Criteria
By: Lou Angelucci
loua2000_99@yahoo.co
m
267-798-9930
Where do we Start
O In order to accept something as a criteria we
need to start with a requirement
O Requirements can be specifications
O Specifications can be attributes or variables
O Variables – Data that are measured:
O Length, diameter, pH, speed
O Attribute – A quality, not measured as data
O Color, number of something, taste
2
Acceptance Criteria
O Where do we start
O Functional Requirement Specification FRS
O Typically what is requested by the user Documentation
that describes the requested behavior of an
engineering system. The documentation typically
describes what is needed by the system user as well as
requested properties of inputs and outputs
O User Requirements URS
O Generally the first in a series of specification
documents. It provides a high level description of the
user's expectation of the project scope, with emphasis
on product parameters and process performance
parameters.
3
Specification
O
URS
O
O
The User Requirements Specification describes what the user require from the system.
User Requirements Specifications are written early in the validation process, typically
before the system is created. They are written by the system owner and end-users, with
input from Quality Assurance. Requirements outlined in the URS are usually tested in the
Performance Qualification or User Acceptance Testing. User Requirements Specifications
are not intended to be a technical document; readers with only a general knowledge of the
system should be able to understand the requirements outlined in the URS.
FRS
O
The Functional Requirements Specification describes what the system must
do; how the system does it is described in the Design Specification. If a User
Requirement Specification was written, all requirements outlined in the User
Requirement Specification should be addressed in the Functional
Requirements Specification.
O Design specification
O Design Specification Design Specifications describe how a system
performs the requirements outlined in the Functional
Requirements.
4
Other Specification Listed
Definition
A list of requirements that must be satisfied prior to the customer accepting
delivery of the product.
O ASTM/PAT) Numerical limits, ranges, process signatures, or other suitable
measures that are necessary for making a decision to accept or reject the results
of a process, in-process variable, a product or any other convenient subgroups or
manufactured units.
O (ICH Q6B) Numerical limits, ranges or other suitable measures for acceptance of
the results of analytical procedures which the drug substance or drug product or
materials at other stages of their manufacture should meet.
O The criteria a product must meet to successfully complete a test phase or to
achieve delivery requirements.
Publication Source: ISPE Baseline® Guide, Vol. 1: Active Pharmaceutical
Ingredients, Second Edition
O
O
O
(ICH Q7) Numerical limits, ranges, or other suitable measures for acceptance of
test results
(IEEE) (ASTM E 2500) The criteria that a system or component must satisfy in
order to be accepted by a user, customer or other authorized entity.
5
Other Specification Listed
Definition
O Measurable terms under which a test result may be considered
O
O
O
O
acceptable.
Publication Source: ISPE Baseline® Guide, Vol. 3: Sterile
Manufacturing Facilities (First Edition)
(ICH Q6A) Numerical limits, ranges, or other suitable measures
for acceptance of the results of analytical procedures.
The limits of conditions of room critical parameters that may
affect the product quality. These conditions may include
temperature, humidity, and room air quality. For example, if
humidity or particulates are not critical parameters affecting
product quality they are not included in acceptance criteria.
Publication Source: ISPE Good Practice Guide: Heating,
Ventilation, and Air Conditioning (HVAC)
6
Other Specification Listed
Definition
O (IEEE) A document that specifies, in a complete, precise,
verifiable manner, the requirements, design, behavior,
or other characteristics of a system or component, and
often, the procedures for determining whether these
provisions have been satisfied.
O USP) A list of tests, references to analytical procedures,
and appropriate acceptance criteria. It establishes the
set of criteria to which an excipient, drug substance, or
drug product should conform to be considered
acceptable for its intended use. “Conformance to
Specification” means that the excipient, drug
substance, and drug product, when tested according to
the listed analytical procedures, will meet the
acceptance criteria.
7
Other Specification Listed
Definition
O
O
O
(ICH Q7) A list of tests, references to analytical procedures, and appropriate acceptance
criteria that are numerical limits, ranges, or other criteria for the test described. It
establishes the set of criteria to which a material should conform to be considered
acceptable for its intended use. “Conformance to specification” means that the material,
when tested according to the listed analytical procedures, will meet the listed acceptance
criteria.
(ICH Q6A) A list of tests, references to analytical procedures, and appropriate acceptance
criteria which are numerical limits, ranges, or other criteria for the tests described. It
establishes the set of criteria to which a drug substance or drug product should conform
to be considered acceptable for its intended use. "Conformance to specifications" means
that the drug substance and / or drug product, when tested according to the listed
analytical procedures, will meet the listed acceptance criteria. Specifications are critical
quality standards that are proposed and justified by the manufacturer and approved by
regulatory authorities.
(ICH Q6B) A specification is defined as a list of tests, references to analytical procedures,
and appropriate acceptance criteria which are numerical limits, ranges, or other criteria
for the tests described. It establishes the set of criteria to which a drug substance, drug
product or materials at other stages of its manufacture should conform to be considered
acceptable for its intended use. “Conformance to specification” means that the drug
substance and drug product, when tested according to the listed analytical procedures,
will meet the acceptance criteria. Specifications are critical quality standards that are
proposed and justified by the manufacturer and approved by regulatory authorities as
conditions of approval.
8
General Definition
O Specifications
O Documentation which clearly and explicitly
defines the system requirements and
standards to be followed during fabrication
and construction, test requirements,
acceptance criteria and the associated
deliverables.
9
Examples
O Specification example
O Volume
O pH
O ______ VAC ____ Hertz
O Phases
O Amperage
O Pressure
O Acceptance criteria example
O Volume target and range
O pH target and range
O ______ VAC ____ Hertz +/- values
O Phases
O Amperage target and range
O Pressure target and range
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Examples
O Process
O Specification example
O CPP
O Mix speed
O ______ RPM ____ Hertz
O pH
O Homogeneity
O Particle size
O Acceptance criteria example
O CPP target and range
O pH target and range
O ______ RPM +/- RPM ____ Hertz +/- values
O Homogeneity (amount of dispersion
O Particle size nanometer etc. target and range
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Example
O Equipment and Systems
O Specification examples
O
O
Volume
RPM
O ______ VAC ____ Hertz
O Pressure rating ASTM
O Torque specification
O Material of Construction
O Acceptance criteria example
O
O
Volume target and range
RPM target and range
O ______ VAC ____ Hertz +/- values
O Pressure measurement llbs etc target and range
O Torque Foot pound target and range
O Material of construction verification
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Example
O Utilities
O Specification example
O Capacity
O Industry or accepted standard
O Temperature
O Flow
O Pressure
O Acceptance criteria example
O Capacity output target and range
O Industry accepted target and range
O Temperature target and range
O Flow target and range
O Pressure target and range
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Validation Acceptance Criteria
O Validation definition
 1987 Validation Definition
 Establishing documented evidence which provides a
high degree of assurance that a specific process will
consistently produce a product meeting its predetermined specifications and quality attributes.
 (2011) Definition of PV
 Process validation is defined as the collection and
evaluation of data, from the process design stage
throughout production, which establishes scientific
evidence that a process is capable of consistently
delivering quality products.
14
Validation Acceptance Criteria
O “pre-determined specifications and
quality attributes.”
O “data from process design stage
throughout production, which
establishes scientific evidence”
O Acceptance criteria is demonstrating
specifications and attributes with
scientific evidence.
15
Validation Acceptance Criteria
O Scientific evidence demands accuracy,
reliability and most importantly
repeatability
O The scientific method is designed to
demonstrate as well as separate fact from
theory
O Acceptance criteria are fact and need to
be repeatable, hence multiple Validation
runs
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Definition
O Acceptance Criteria
O Numerical limits, ranges, or other suitable
measures (attributes) for acceptance of the
results of analytical procedures which the drug
substance or drug product or materials at other
stages of their manufacture should meet.
O Specified indicators or measures employed in
assessing the ability of a component, structure
or system to perform its intended function.
17
Validation Acceptance Criteria
O Acceptance criteria is something we need to
measure, verify and/or achieve to show
compliance to a specification or
specifications
O Specification is a definition of the minimum
requirements and properties of a process,
equipment or system.
18
Validation Acceptance Criteria
O Acceptance criteria then are derived from
specifications that are designed and built
into the equipment, system or product and
verified and documented through the
activities we call qualification and
validation.
19
Validation Acceptance Criteria
O Do all specifications have to be verified or
qualified?
O How do we determine which ones then?
O Criticality assessment
O FDA accepts the concept
O Need to provide justification and
rationalization
O Techniques of criticality assessment is a
separate topic and lecture.
20
Criticality Assessment
Summary
O Document Risk Assessment Reference
o FDA 2004: Pharmaceutical cGMPs for the 21st Century –
A Risk Based Approach
o
o
“Encourages implementation of risk-based approaches”
http://www.fda.gov/downloads/Drugs/DevelopmentApprovalPro
cess/Manufacturing/QuestionsandAnswersonCurrentGoodMan
ufacturingPracticescGMPforDrugs/UCM176374.pdf
o FDA 2006: Guidance for Industry – [ICH] Q9 Quality Risk
Management
o Perform risk assessments at appropriate stages to
evaluate the risks to product quality and patient safety
o http://www.fda.gov/downloads/Drugs/.../Guidances/ucm
073511.pdf
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Risk Assessment Tools
O Risk Matrix
O PHA= Preliminary Hazard Analysis
O FTA=Fault Tree Analysis
O FME(C)A=Failure Mode Effects
(Criticality) Analysis
O HAZOP=Hazard Operability Analysis
O HACCP=Hazard Analysis and Critical
Control Point
22
FME(C)A
O Most often used for qualified equipment
and systems as well as validated
processes.
O Definition
O Failure mode, effects and criticality
analysis (FMECA) is an extension of failure
mode and effects analysis (FMEA). FMEA
is a bottom-up, inductive analytical method
which may be performed at either the
functional or piece-part level.
23
Create SOD Tables
O Severity (S)
O Link to end product functional failure
O Medical Department involvement
O Occurrence (O)
O Use historical data
O Similar processes products
O Detection (D)
O Method validation studies
O Historical data
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FMEA Model
POTENTIAL FAILURE MODE AND EFFECTS ANALYSIS
X-Ray ZM Device
Subsystem
Component ____________________
Process
FMEA Number
Page
of
Prepared By
FMEA Date (Orig.)
Responsibility
(rev.)
Core Team:
_______________________________________________________________________________________________
Device/
Function
Potential
Failure
Mode
Potential
Effect(s)
of Failure
S
Potential
Cause(s)
of Failure
O
Treatment
setup time
increases
2
Burn Out
Bulb
4
Current
Controls
D
R
P
N
Recommended Responsibility Action Results
Action(s)
and Target
Actions
R
Complete Date Taken S O D P
N
Field Defining
Light
Visible Treatment
Field Indication
1) Light
Failure
2)
Alignment
Failure
4 32 -Better light
source
-Redundant
source
-Quick change
light bulb
3
a) light
source
moved
1
4 12
3
b) Mirror
moved
5
4 60
Wrong Field
Defined
Causing
Repeat xrays and
additional
setup time
2 3 4 24
1 1 2
2
1 1 4
4
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Risk Assessment Tools
Risk Assessment Document
Step
Process
Failure Mode Hazard
Collect Water @
126 drop / WFI
High Count/ obj
4.1 System
organism
(Processing tank
#1,2,3)
•
•
•
Potential
Cause
Existing controls
Detection
ECP ECP
Method Sev Prob Det Y/N Where
WFI System Validation,
SOP (equipment,
Infection
preventive maintenance,
requiring WFI System
USP / EP
manual cleaning,
medical
failure
water test,
manufacturing, training,
intervention
environmental,
procedures)
10
8
3
YES
USP Test
Procedure
Essential Control Points (ECP) based on ratings
The C in FMECA
Result: Demonstrate through Acceptance Criteria
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Flow chart to Acceptance Criteria
Begin
Requirements
Yes
FRS/URS
Yes
No criticality
assigned
No
Risk
Assessment
yes
SOD (RPN)
determines
criticality
Yes
List as non
essential or noncritical
Acceptance
Criteria
Development
Assign Criticality
to the
Item or measure
END
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Acceptance Criteria
O Essential Control Points (ECP)
O These become CPPs (Critical Process Parameters)
O A process parameter that must be controlled within
predefined limits to ensure the product meets its
pre-defined quality attributes
O They also become CQAs (Critical Quality
Attributes)
O A quality attribute that must be controlled within
predefined limits to ensure that the product meets
its intended safety, efficacy, stability and
performance
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Conclusions
Acceptance Criteria
• Need to be spelled and met as part of the qualification
protocol
• Should be stated in a general sense with the applicable VMP
• With some protocols the requirement is stated with a
reference to A standard or specification
• Possible that some Acceptance Criteria may not have a
direct
Specification
• They may be general and non specific with no true ability to
Measure a value
• These would be general attribute criteria
• All are derived from Specifications, critical parameters and
quality attributes.
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Questions
www.globalcompliancepanel.com
30
Thank you
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www.globalcompliancepanel.com
Interactive 1
What specifications should we have in place
32
Interactive 1
Specifications
Specifications
1.____________
6.____________
2.____________
7.____________
3.____________
8.____________
4.____________
9.____________
5.____________
10.___________
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Interactive 1
Suggestions:
1.
2.
3.
4.
5.
6.
7.
Time dependent toasting 30 sec. to 1 minute
Selective shade of toasting
Independent controls
Working voltage 120Vac 60 Hz.
Coil Temperature 120 degree ◦F to 180 ◦F
Safety (burn potential) Housing temperature
Insulation from heat chamber fiberglass ½
inch thick with air break
8. Safety and user requirements
34
Interactive 1
For the same system item what would be our Acceptance
criteria?
35
Interactive 1
Acceptance
Criteria
Acceptance
Criteria
1.____________
6.____________
2.____________
7.____________
3.____________
4.____________
8.____________
9.____________
5.____________
10.___________
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Interactive 1
Acceptance Criteria Suggestions:
1.
2.
3.
4.
5.
6.
7.
Timer to calibrated 30 seconds to 1 minute +/- 1 second
Temperature setting per toast shade
Input voltage 120 +/- 5 volts AC 60 Hertz +/- 1 Hz
Outer shell housing temperature < 80 ◦F
Push button selection
Independence of each side
Ease of Toast ejection
37
Interactive 2
What specifications should we have in place for USP Water?
USP
38
Interactive 2
Specifications
Specifications
1.____________
6.____________
2.____________
7.____________
3.____________
8.____________
4.____________
9.____________
5.____________
10.___________
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Interactive 2
Suggestions:
1. Conductivity <1.3 uS/cm at 25 C
2. Bacterial Colonies <100 cfu/ml
3. pH 5.0 to 7.0
4. TOC < 500 ug/L (500 ppb)
5. Nitrates EP <0.2 ppm
6. Heavy Metals EP <0.1 ppm
7. Reynolds number for turbulent flow >4000
8. Method of sanitization recommendation TBD
9. Monitoring criteria
10.Seasonal Testing recommendations
40
Interactive 2
For the same system item what would be our Acceptance
criteria?
USP
41
Interactive 2
Acceptance
Criteria
Acceptance
Criteria
1.____________
6.____________
2.____________
7.____________
3.____________
4.____________
8.____________
9.____________
5.____________
10.___________
42
Interactive 2
Acceptance Criteria Suggestions:
1.
2.
3.
4.
Same as specifications
Seasonal Testing
Periodic monitoring
Sanitization requirement
43
Interactive 3
What specifications should we have in place for this architectural
structure?
44
Interactive 3
Specifications
Specifications
1. ______________
6. ______________
2. ______________
7. ______________
3. ______________
8. ______________
4. ______________
9. ______________
5. ______________
10. _____________
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Interactive 3
Suggestions:
1. Concentric
2. Drop lines radially spaced
3. Spiral arms equal distant
4. Spiral Arms tacky drop lines not
5. Repairable
6. Translucent color
7. Wind and rain resistant
8. Tensile strength
9. Elastic and Pliable
10. Exponential spiral equation
11. Materials of construction
46
Interactive 3
For the same system item what would be our Acceptance criteria?
47
Interactive 3
Acceptance
Criteria
Acceptance
Criteria
1.____________
6.____________
2.____________
7.____________
3.____________
4.____________
8.____________
9.____________
5.____________
10.___________
48
Interactive 3
Suggestions:
1. Measure of concentricity
2. Exponential spacing of radial drop lines
3. Spiral distance __mm + .1mm
4. PM Schedule
5. White to translucent color (Pantone color
standard)
6. Surface tension value γ = F/L
7. Max wind speed and force
8. Spring force for elasticity Hook’s Law
10. x²+y² = a²[arc tan (y/x)]² spiral equation
11. 20 standard amino acids
(42% glycine and 25% alanine as the major amino acids)
49