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Critical Parameters Affecting Process Validation
Validation is an integral part of quality assurance; it involves
systematic study of systems, facilities and
processes aimed at determining whether they perform their
intended functions adequately and
consistently as specified. Validation in itself does not improve
processes but confirms that the
processes have been properly developed and are under control.
Adequate validation is beneficial to the
manufacturer in many ways It deepens the understanding of
processes; decreases the risk of preventing problems, defect costs,
regulatory non compliances and thus assures the smooth running
of
the process.
Process Validation is key to a robust manufacturing process
Process validation involves a series of activities taking place
over the lifecycle of product and process.
Validation requires a meticulous preparation and careful
planning of the various steps in the process.
All work involved should be carried out in a structured way
according to formally authorized
standardized working procedures.
1. What are the Critical Parameters affecting Process
Validation? The critical parameters should normally be identified
during the development stage or from historical
data or during manufacturing and process control. Process
validation involves three stages and now
will identify the critical parameters in these stages.
2. Stage One: Process Design Process design is the activity of
defining the commercial manufacturing process. The goal of this
stage
is to design a process suitable for routine commercial
manufacturing that can consistently deliver a
product that meets its critical quality attributes. A product
development activity provides key inputs to
the design stage, such as the intended dosage form, the quality
attributes, and a general manufacturing
pathway. The functionality and limitations of commercial
manufacturing equipment should be
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considered, also contributions of variability by different
component lots, production operators,
environmental conditions and measurement systems in the
production setting.
Designing an efficient process with an effective process control
approach is dependent on the process
knowledge. Use of risk analysis tools to screen potential
variables for Design of Experiment (DOE)
studies to minimize the total number of experiments. The results
of DOE studies can provide
justification for establishing ranges of incoming component
quality, equipment parameters and in-
process material quality attributes. Manufactures should
document the variables studied for a unit
operation and the rationale for those variables identified as
significant. This information is useful
during the process qualification and continued process
verification stages, including the design is
revised or strategy for control is refined.
Process control addresses the variability to assure quality of
the product. Controls can consists of
material analysis and equipment monitoring at significant
processing points designed to assure that the
operation remains on target and in control with respect to
output quality. Timely analysis, control and
adjust the processing conditions so that the output remains
constant.
3. Stage Two: Process Qualification During this stage, the
process design is confirmed as being capable of reproducible
commercial
manufacturing. It confirms that all established limits of the
critical parameters are valid and that
satisfactory products can be produced even under worst case
condition. This stage has following
elements Qualification of Utilities and Equipment.
Installation Qualification is an essential step preceding the
Process Validation exercise which is
normally executed by Engineering group. The installation of
equipment should follow well defined
plans which is developed and finalized following progression
through a number of design stages. This
stage of validation includes examination of Equipment Design,
Determination of Calibration,
Maintenance and Adjustment Requirements.
Consider the following Equipment Calibration Requirements
1. Confirmation of calibration of calibrating equipment with
reference to the appropriate national
standard.
2. Calibration of measuring devices utilized in the Operational
Qualification stage.
3. Identification of calibration requirements for measuring
devices for the future use of the equipment.
At the Installation Qualification stage the company should
document preventive maintenance
requirements for installed equipment.
Operational Qualification is an exercise oriented to engineering
function referred as commissioning. It
is important stage to assure all operational test data conform
with pre-determined acceptance criteria
and manufacturer should develop draft standard operating
procedures for the equipment, service
operation, cleaning activities, maintenance requirements and
calibration schedules.
The critical operating parameters for the equipment or the plant
should be identified at the Operational
Qualification stage. Critical variables should incorporate
specific details and tests that have been
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developed. The completion of a successful Operational
Qualification should include the finalization of
operating procedures and operator instructions documentation for
the equipment.
Performance Qualification combines the actual facility,
utilities, equipment, trained personnel, control
procedures and components to produce commercial batches.
Performance qualification will have a
higher level of sampling, additional testing and greater
scrutiny of process performance. The level of
monitoring and testing should be sufficient to confirm uniform
product quality throughout the batch
during process.
4. Stage Three: Continued Process Verification Continually
assure that the process remains in a state of control during
commercial manufacturing. A
system or systems for detecting unplanned departures from the
process as designed is essential. The
following points to be considered in Continued Process
Verification.
Collection and evaluation of information and data about the
performance of the process will allow
detection of process drift. Evaluation should determine whether
action must be taken to prevent the
process from drifting out of control.
An ongoing program to collect and analyze product and process
data that relate to product quality must
be established to verify the critical quality attributes are
being controlled throughout the process.
Process variation also can be detected by assessment of defect
complaints, out of specifications finding,
process deviation reports, process yield variations, batch
records, incoming raw material records and
adverse event reports.
Operators errors should be tracked to measure the quality of the
training program. Maintenance of the facility, utilities and
equipment is an important aspect of ensuring that a process
remains in control.
5. Conclusion Process validation is a mean of ensuring and
documenting that the processes are capable of producing a
finished product of the required quality consistently and should
cover all the critical elements of the
manufacturing process. The process design stage and the process
qualification stage should have as a
focus the measurement system and control loop establishing
scientific evidence that the process is
reproducible and will consistently deliver quality products.
Good process design and development should anticipate
significant sources of variability and establish
appropriate detection, control, appropriate alert and action
limits. Process variability should be
periodically assessed. It is the responsibility of the
manufacturer to judge and provide evidence of a
high degree of assurance in its manufacturing process.
6. References
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Guidance for Industry Process Validation: General Principles and
Practices US Dept. of Health and Human Services, Food and Drug
Administration. Nov. 2008 Current Good
Manufacturing Practices.
ANNEX 15. Validation Master Plan, Design Qualification,
Installation and Operational
Qualification, Non Sterile Process Validation, Cleaning
Validation. 17th Sep. 1999.
7. Author Rajkumar P. Patil
Sr. Production Officer
Mobile No. +919945642935
Mail ID. [email protected]
