Process Validation

By Ron Weber
Device Specialist
Florida District Office

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Purpose & Scope

Definition
History
Importance

for SUDs
Reprocessors
Overview
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Process Validation

Definition

1987 Guidance - Establishing documented evidence

which provides a high degree of assurance that a
specific process will consistently produce a
product meeting its pre-determined specifications
and quality characteristics.
GHTF - Documented procedure and process for
obtaining, recording and interpreting the results
required to establish that a process will consistently
yield product complying with predetermined
specifications.

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Process Validation
Quality System Definition:
ESTABLISHING by objective evidence

that a
process
consistently produces a
result or
product
meeting its
predetermined
specifications.

Define
Define
Document
Document
Implement
Implement
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Monitoring & Control

Establish and maintain procedures to

ensure that the specified requirements
continue to be met.
[21 CFR 820.75(b)(1)]
Management of applied process
parameters [APP]
Six Sigma
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APP/Rejects
Loose controls
= high rejects

L
e
s
s

A
P
P
REJECT RATE

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Common Denominator

ZERO
DEFECTS

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History

Birth in Aerospace Industry

Increase in Recalls during 1980s

1987 Guidance Document (http://www.fda.gov/cdrh/ode/

425.pdf)
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Good Guidance
Practices
This guidance was written prior to the February
27,1997 implementation of FDAs Good Guidance
Practices, GGPs. It does not create or confer rights
for any or on any person and does not operate to bind
FDA or the public. An alternative approach may be
used if such approach satisfies the requirements of
the applicable statute, regulation, or both. This
guidance will be updated in the next revision to
include the standard elements of GGPs.
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Importance

Increased control of process

Increase production of higher
quality devices - Ex: IOLs
Confirm Process Design
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Processes to Validate
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.
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Validation - Verification
Validation - Confirmation by
examination and provision of object
evidence that the particular
requirements for a specific
intended use can be consistently
fulfilled.
Verification - Confirmation by
examination and provision of objective
evidence that specified requirements
have been fulfilled.
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Is Process
Output
Verifiable?

Is verification
Sufficient &
Cost Effective?

Yes

No

Yes

Verify &
Control the
Process?

No

What is level of
RISK TO
PATIENT?

Accept Risk
of Limited
Process
Control

LOW
OPTIONS

Validate for
Business
Reasons

HIGH OPTIONS

Validate to
Control
RISK

Redesign
Product and
/or Process

Process Validation
Decision Tree

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Processes that
should be Validated
Sterilization
Process & Test Software
Clean Room Ambient Conditions
Aseptic filling processes
Sterile packaging sealing processes
Lyophilization process

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Processes which may be

satisfactorily verified

Manual cutting process

Testing for color, turbidity, pH

Visual inspection of PCBs

Manufacturing and testing of

wiring harnesses
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Use Decision Tree

Cleaning processes
Certain Human assembly
processes
Filling process
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5. Process Monitoring
4. Process/Product
Qualification

6. Revalidate

Process
Validation

1. Planning

3. Operational
Qualification
2. Installation
Qualification

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Protocol

A written plan stating how

validation will be conducted,
including test parameters,
product characteristics,
production equipment, and
decision points on what
constitutes acceptable test
results.
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Installation
Qualification(IQ)
Ensure that all equipment used in
manufacturing, including ancillary
systems, meets specified
requirements and is appropriately
designed, constructed, placed and
installed to facilitate maintenance,
adjustment, cleaning, and use.[21 CFR 820.70(g)]
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Operational
Qualification (OQ)
Establishing parameters by
objective evidence which result
in product that meets all
predetermined requirements.
Shows that the equipment
operates properly and
determines optimal process
settings.

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OQ
Determine if process is capable

Does it operate within specified

parameters?
Does it produce a product or
result that meets specifications?
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OQ
Develop, conduct, control, and
monitor production processes to
ensure that a device conforms to its
specifications. [21 CFR820.70(a)]
Establish and maintain process
control procedures that describe any
process controls necessary to ensure
conformance to specification.

[21 CFR820.70(a)]
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Performance
Qualification (PQ)

Establish by objective evidence

that the process, under
anticipated conditions,
consistently
produces a product
which meets all
predetermined
requirements.
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PQ

Performance qualification
involves repetitive testing
(multiple batches) to show that
the process will consistently
result in a product meeting
specifications (including
product testing under simulated
use conditions, if applicable).
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PQ

The confidence in the process is

augmented by increasing the number
of batches run and the number of
samples tested.

The reliability and consistency of the

process can be shown by performing
statistical calculations.
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Non-conformities
Non-conformities often occur
because of errors made and
because of excessive variation.
Many non-conformities are not
the result of errors but the
result of EXCESSIVE VARIATION
AND OFF-TARGET PROCESSES

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Unstable Process
It must be
FDAs fault!

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Stable Process
I tamed the
process. How
about a raise?

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Strategies & Tools for reducing

variation and Optimizing the
process Average

Mistake Proofing
Capability Study
Challenge Tests
Acceptance
Sampling Plans
Component
Swapping Study
Control Charts

Analysis of Means
Analysis of
Variation
Failure Mode and
Effects Analysis
Fault Tree Analysis
Robust Design
Methods

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Capability Study

Measures the ability of the process to

consistently meet the specification.
Frequently used towards the end of
validation to demonstrate that the
products consistently meet the
specifications
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Capability Study

Performed by selecting a small

number of units periodically over
time
Averages and ranges are plotted
over time using a control chart to
determine if the process is stable.
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A capability study is used to

determine whether a process
is stable and capable.

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Documentation

Master Validation Protocol or

Plan
Protocols or Plans for:
Installation Qualification
Operational Qualification
Performance/Product Qualification
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Documentation

Data Collection and Analyses

Final Report - deviations,
conclusions and approval
Dont forget: Acceptance
Criteria for successful study
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I didnt know we
needed them.

Software

When computers or automated data

processing systems are used as a part
of the production or the quality system,
the manufacturer shall validate
computer software for its intended use
according to an established protocol.
All software changes shall be validated
before approval and issuance. [21
CFR820.70(I)]

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Software

The output of the process may

be fully verifiable and the
overall process may not require
validation however software
used for automation or testing
such processes should always
be validated for its intended
use.
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