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Overview of Regulation
FDA 483 Trends specific to Process Validation
Inspection Process
M. Wilkins April
2004 2
Process Validation
§820.3(z) – Validation
Means confirmation by examination and provision
of objective evidence that the particular
requirements for a specific intended use can be
consistently fulfilled
M. Wilkins April
2004 3
Process Validation
M. Wilkins April
2004 4
Process Validation
§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
M. Wilkins April
2004 5
When is 820.75(a) Applicable?
M. Wilkins April
2004 6
Question
M. Wilkins April
2004 7
Process Validation
§820.75(b)
Each manufacturer shall establish and maintain
procedures for monitoring and control of process
parameters for validated processes to ensure
that the specified requirements continue to be
met
M. Wilkins April
2004 8
Process Validation
§820.75(b)(2)
For validated processes, the monitoring and
control methods and data, the date performed,
and, where appropriate, the individual(s)
performing the process or the major equipment
used shall be documented
M. Wilkins April
2004 9
When is 820.75(b) Applicable?
M. Wilkins April
2004 10
Question
M. Wilkins April
2004 11
Preamble Comment 145
M. Wilkins April
2004 12
Process Validation
§820.75(c)
When changes or process deviations occur, the
manufacturer shall review and evaluate the
process and perform revalidation where
appropriate
M. Wilkins April
2004 13
When is 820.75(c) Applicable?
Process changes
Equipment changes
Product (design) changes
Process deviations
M. Wilkins April
2004 14
Question
M. Wilkins April
2004 15
Preamble Comment 125
M. Wilkins April
2004 16
Preamble Comment 4
M. Wilkins April
2004 17
Question
M. Wilkins April
2004 18
Process Changes
M. Wilkins April
2004 19
FDA-483 Trends
Document Management
Controls Controls
4% 20%
P&PC
36%
Design
Controls
11%
CAPA
29%
M. Wilkins April
2004 21
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P&PC Subsystem Observations
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M. Wilkins April
22
Observations for 21 CFR 820.75
October 2000 to March 2004
820.75(c),
24
820.75(b),
59 820.75(a)
820.75(b)
820.75(c)
820.75(a),
269
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2004 23
Process Validation Observations
M. Wilkins April
2004 24
Process Validation Observations
21 CFR 820.75(a) = 88
Documentation - general
Process validation activities and results have not
been [fully] documented
M. Wilkins April
2004 25
Process Validation Observations
21 CFR 820.75(b) = 40
Monitoring and control
Procedures were not [established] [defined]
[documented] [complete] [implemented] for
monitoring and control of process parameters for
validated processes
M. Wilkins April
2004 26
Process Validation Observations
21 CFR 820.75(b)(2) = 16
Documentation of validated process
performance
There is no documentation of [monitoring and
control methods and data] [the major equipment
used] for a validated process
M. Wilkins April
2004 27
Process Validation Observations
21 CFR 820.75(c) = 13
Documentation – review in response to
changes
There is no documentation of the [review and
evaluation of a process] [revalidation of a
process] conducted in response to changes or
process deviations
M. Wilkins April
2004 28
Process Validation Observations
21 CFR 820.75(c) = 11
Process changes – review, evaluation and
revalidation
A validated process was not [reviewed and
evaluated] [revalidated] when changes or process
deviations occurred
M. Wilkins April
2004 29
Process Validation Observations
21 CFR 820.75(a) = 6
Documentation – specific items
Documentation of process validation activities
and results does not include [the date and
signature of the individuals approving the
validation] [the major equipment validated]
M. Wilkins April
2004 30
Process Validation Observations
21 CFR 820.75(b)(1) = 3
Performed by qualified individual
A validated process was not performed by a
qualified individual
M. Wilkins April
2004 31
Process Validation Observations
M. Wilkins April
2004 34
Inspection Process
M. Wilkins April
2004 36
Management Controls Subsystem
M. Wilkins April
2004 37
Design Control Subsystem
M. Wilkins April
2004 38
Package Materials and Design
Requirements to consider
Permeability
Microbial barrier properties
Formation of toxins during processing
Interaction between products and package
materials
Chemical properties – pH value, chloride and
sulfate content
Labeling of package
M. Wilkins April
2004 39
Package Materials & Design
Requirements to consider
Physical properties – tensile strength, thickness
variation, tear variation, burst strength
Adhesive, coated materials – coating patterns,
minimum specified seal strength
M. Wilkins April
2004 40
Design Control Subsystem
M. Wilkins April
2004 41
Design Control Subsystem
M. Wilkins April
2004 42
Corrective & Preventive Actions
(CAPA) Indicators
Complaints
Open packages
Poor seal
Tears
Loss of sterility
Infections
Foreign objects
M. Wilkins April
2004 43
CAPA Indicators
M. Wilkins April
2004 45
Inspection Process - P&PC
M. Wilkins April
2004 46
Inspection Process
Purchasing controls
Supplier evaluation and approval
Material specifications/changes
Packaging process validation
Installation Qualification
Operational Qualification
Performance Qualification
M. Wilkins April
2004 47
Validation Deficiencies
M. Wilkins April
2004 48
Validation Deficiencies
M. Wilkins April
2004 49
Packaging Process Deficiencies
M. Wilkins April
2004 50
Packaging Process Deficiencies
M. Wilkins April
2004 51
Packaging Process Deficiencies
M. Wilkins April
2004 52
Questions
M. Wilkins April
2004 53