4/1/2020
Summary of Process Validation
Dr. Fayez Abou Hamad
MDV-Solve
Process Validation - Basics
Process Validation is required according to:
✓ 11 CFR Part 820.75
✓ 11 CFR Part 820.70 (software validation)
✓ EN ISO 13485 (7.5.2)
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Process Validation - Basics
Definition:
“Where the result 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.”
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Process Validation - Basics
S Redesign product
or process
Is process output N Redesign product Y
fully verifiable ? or process possible ?
Is verification sufficient N N
& Cost effective ?
Y
Verify and Control Validate
the process the process
> Quality Controle > Quality Assurance
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MDV-Solve 4
Process Validation - Basics
✓Definition
Establish 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.
Establish (21CFR820.3(k)) :
- define : Prepare a validation protocol
- implement : Execute the protocol
- document : Gather evidence
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MDV-Solve 5
Process Validation - Basics
✓Definition
Establish 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.
Evidence :
- “What’s not documented is not done...”
- ...but what’s not documented properly is useless...
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MDV-Solve 6
Process Validation - Basics
✓Definition
Establish 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.
A high degree of assurance :
- 100% proof is not possible
- identify / quantify potential risks
- quantify impact of the risks
> “Risk based approach” !!
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MDV-Solve 7
Process Validation - Basics
✓Definition
Establish 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.
consistently produce :
- Based on statistics
- Gauss-curve
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MDV-Solve 8
Process Validation - Basics
✓Definition
Establish 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.
predetermined specifications :
- Process description
- Critical process parameters
- Acceptance criteria
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Process Validation - Basics
Perform criticality assessment where all process steps are
summarized from the product standard and corresponding
process flow.
Process steps are compared with the risk analysis of the
product and all process steps are divided into criticality
category
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Process Validation - Basics
Process steps - criticality classifications:
category I: processes linked in the risk analysis to high
moderate harm & servility.
category II: processes linked in the risk analysis to high low &
servility.
category III: All remaining process steps, without non impact
product changes. This category includes also processes which
are fully (100%) verified by consequent inspection and testing
Processes business risk, can be included in any category
rigidness the severity
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Process Validation - Basics
Process Validation - phases
Installation qualification (IQ): establishing by objective evidence that all key aspects
of the process equipment and ancillary system installation adhere to the
manufacturer’s approved specification and that the recommendations of the
supplier of the equipment are suitably considered.
Operational qualification (OQ): establishing by objective evidence process control
limits and action levels which result in product that meets all predetermined
requirements.
Performance qualification (PQ): establishing by objective evidence that the process,
under anticipated conditions, consistently produces a product which meets all
predetermined requirements.
PRE- APPROVED PROTOCOLS
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Process Validation - Basics
Installation qualification (IQ) – Static
IQ means is it installed correctly -- VERIFY:
Equipment design features (i.e. materials of construction
cleanability, etc.)
Installation conditions (wiring, utilities, functionality, etc.)
Calibration, preventative maintenance, cleaning schedules, Spare
parts list
Safety features
Supplier documentation, prints, drawings and manuals
Software documentation
Environmental conditions (such as clean room requirements,
temperature, humidity)
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Process Validation - Basics
Operational Qualification (OQ)
Process control limits (time, temperature, pressure, lines
peed, setup conditions, etc.)
Software parameters
Raw material specifications
Process operating procedures, Process change control
Training
Short term stability and capability of the process (control
charts) - Also under worst-case conditions
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Process Validation - Basics
Performance Qualification - (PQ)
key objective is to demonstrate the process will
consistently produce acceptable product under normal
operating conditions.
PQ include at least 3 consecutive production run:
▪ Actual product and process parameters and procedures
established in OQ
▪ Acceptability of the product
▪ Assurance of process capability as established in OQ
▪ Process repeatability, long term process stability
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Process Validation - Basics
Statistical tools for process validation
Capability study:
Measures the ability of the process to consistently meet the
specifications.
Testing should be performed not only at nominal, but also
under worst-case conditions.
Acceptance sampling plans can be useful in optimizing the
number of samples to be tested and to demonstrate
conformance to specification.
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Process Validation - Basics
Stable processes produce a consistent level of
performance.
The total variation is reduced.
The process is more predictable
Once a consistent performance has been achieved,
the remaining variation must be made to safely fit
within the upper and lower specification limits.
Such a process is then said to be stable and capable.
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Process Validation - Basics
Normal curve applied to histogram
Average - 3 Std. Dev. Average Average + 3 Std. Dev.
99.73%
The standard deviation represents the typical distance a unit is from the average
For the normal curve, 99.73% of the units fall within 3 standard deviations of the average.
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Process Validation - Basics
Histogram of data
LSL USL
3
Number
2
0
95 100 105
Length (cm)
The width of the histogram represents the variation. interest is whether the histogram is
properly centered and whether the histogram is narrow enough to easily fit within the
specification limits. The center of the histogram is estimated by calculating the average of
the 12 readings
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Process Validation - Basics
Example:
one operation involves cutting wire into 100 cm lengths. The tolerance is
100 5 cm. A sample of 12 wires is selected at random and the
following results obtained:
98.7, 99.3,100.4,97.6,101.4,102.0, 100.2, 96.4,
103.4,102.0,98.0,100.5
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Process Validation - Basics
UNSTABLE PROCESS
Total
Variation
e
m
Ti
Example unstable process. The process is constantly changing. The average shifts up and
down. The variation increases and decreases. The total variation increases due to the
shifting.
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MDV-Solve 21
Process Validation - Basics
STABLE PROCESS
Total
Variation
e
m
Ti
Example stable process. Stable processes produce a consistent level of performance. The
total variation is reduced. The process is more predictable
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MDV-Solve 22
Process Validation - Basics
P R O C E SS C A P A B IL ITY
CA P AB LE
NOT Spec
L im its
C A P A B LE
e
m
Ti
Once a consistent performance has been achieved, the remaining variation
must be made to safely fit within the upper and lower specification limits.
Such a process is then said to be stable and capable.
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MDV-Solve 23
Process Validation - Basics
Control Chart
Once a consistent performance has been achieved, the remaining variation
must be made to safely fit within the upper and lower specification limits.
Such a process is then said to be stable and capable.
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MDV-Solve 24
Process Validation - Basics
Final report
At the conclusion of validation activities, a final
report should be prepared.
summarize and reference all protocols and results.
derive conclusions regarding the validation status of the
process.
The final report should be reviewed and approved by the
validation team and appropriate management
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Process Validation - Basics
Maintaining a state of validation
Monitor and control
Process trending monitored to ensure the process remains within the established
parameters.
When monitoring data on quality characteristics demonstrates a negative trend,
the cause should be investigated, corrective action may be taken and revalidation
considered.
Changes in processes and/or product
Any changes in the process and /or product including changes in procedures,
equipment, personnel, etc. should be evaluated to determine the affects of those
changes and the extent of revalidation considered.
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Process Validation - Basics
Sample protocols
01/04/202
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QUESTIONS
THANK YOU
01/04/202
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