Validation
Objective
• At the end of this session , student
will be able to
• Explain different types of validation and its importance
• Describe validation master plan
Validation
• Validation
is a key process for effective quality assurance
• Validation is establishing
documented evidence which provides a high degree of assurances
• That a specific process or equipment
will consistently produce a product
• Or result meeting its predetermined
specifications and quality attributes
The Major Reasons for Validation
Quality assurance:
Validation checks the accuracy and reliability of a system
or a process to meet the predetermined criteria. A successful validation
provides high degree of assurance that a consistent level of quality is
maintained in each unit of the finished product from one batch to another batch
Economics:
Due to successful validation, there is a decrease in
sampling and testing procedures and there are less number of product rejections
and retesting. This leads to cost-saving benefits
Compliance:
For
compliance to current good manufacturing practices validation is essential
Documentation
• Documentation
associated with validation includes
• Standard
operating procedures (SOPs)
• Specifications
• Validation master plan (VMP)
• Qualification
protocols and reports
• Validation
protocols and reports
Types of Validation
• Prospective validation (also called
premarket validation)
• Retrospective validation
• Concurrent validation
• Re-validation
Prospective Validation
• Conducted prior to the distribution
of either a new product
• A product made under a modified
production process
• Where the modifications are
significant and may affect the product’s characteristics
It is a pre-planned scientific approach. and
includes:
• The
initial stages of formulation development
• Process
development
• Setting
of process specifications
• Developing
in-process tests
• Sampling
plans
• Designing
of batch records
• Defining
raw material specifications
• Transfer
of technology from scale-up batches to commercial
• size
batches
• Listing
major process equipment and environmental controls
The Implementation of Validation work Requires
Considerable Resources
• Time:
generally validation work is subject to rigorous time schedules
• Financial:
validation often requires the time of specialized personnel and expensive
technology
• Human:
validation requires the collaboration of experts from various disciplines
• e.g.
a multidisciplinary team, comprising quality assurance, engineering,
manufacturing and other disciplines, depending on the product and process to be
validated
Retrospective Validation
• The
retrospective validation option is chosen for established products whose
manufacturing processes are considered stable. and when on the basis of
economic considerations alone and resource limitations, prospective validation
programs cannot be justified
• Wherein
the numerical in-process and/or end-product test data of historic production
batches are subjected to statistical analysis
Using either data-based computer systems or manual
methods, retrospective validation may be conducted in the following manner:
- Gather
the numerical data from the completed batch record and include assay
values, end-product test results, and in-process data - Organize
these data in a chronological sequence according to batch manufacturing
data, using a spreadsheet format - Include
data from at least the last 20–30 manufactured batches for analysis - Trim
the data by eliminating test results from noncritical processing steps and
delete all gratuitous numerical information - Subject
the resultant data to statistical analysis and evaluation - Draw
conclusions as to the state of control of the manufacturing process based
on the analysis of retrospective validation data. - Issue
a report of your findings (documented evidence)
Retrospective Validation
• One
or more critical measured responses being evaluated, and selected for statistical
analysis.
• Solid
Dosage Forms
• Content
uniformity testing
• Hardness
values
• Thickness
values
• Weight
variation
• Dissolution
time or disintegration time
• Moisture
content
• Semisolid
and Liquid Dosage Forms
• pH
value (aqueous system)
• Viscosity
• Density
• Color
or clarity values
• Average
particle size or distribution
• Unit weight variation and/or potency values
Concurrent Validation
- A
process where current production batches are used to monitor
processing parameters - It
gives assurance of the present batch being studied
Note: offers limited assurance regarding consistency of
quality from batch to batch
Re-validation
Required when there is a change in:
• Any
of the critical process parameters
• Formulation
• Primary
packaging components
• Raw
material fabricators
• Major
equipment or premises
• Failure
to meet product specifications and process specifications in sequential batches
Calibration
• The
set of operations that establish, under specified conditions
• The
relationship between values indicated by an instrument or system for measuring
• For
example, weight, temperature and ph
Recording
controlling
• The values represented by a material measure,
• The
corresponding known values of a reference standard.
• Limits
for acceptance of the results of measuring should be established
Computer
Validation
• Documented
evidence which provides a high degree of assurance
• Computerized
system analyses
• Controls
and records data correctly
• Data
processing complies with predetermined specifications
Commissioning
• The
setting up, adjustment and testing of equipment or a system
• To
ensure that it meets all the requirements
• As
specified in the user requirement
• Capacities
as specifi ed by the designer or developer
• Commissioning
is carried out before qualifi cation and validation
Concurrent Validation
• Validation
carried out during routine production of products intended for sale
Cleaning Validation
• Documented
evidence to establish
• cleaning
procedures are removing residues to predetermined levels of acceptability
• Taking
into consideration
• Factors
such as batch size, dosing, toxicology and equipment size
Design Qualification (DQ)
• Documented
evidence that the premises, supporting systems, utilities, equipment
• Processes
have been designed in accordance with the requirements of GMP
Good Engineering Practices (GEP)
• Established
engineering methods and standards
• that
are applied throughout the project life-cycle to deliver appropriate,
cost-effective solutions
Installation Qualification (IQ)
• The
performance of tests to ensure that the installations
• Such
as machines,measuring devices, utilities and manufacturing areas
• Used
in a manufacturing process are appropriately selected and correctly installed
• Operate
in accordance with established specifications
Operational Qualification (OQ)
• Documented
verification that the system or subsystem performs
• As
intended over all anticipated operating ranges
Performance Qualification (PQ)
• Documented
verification that the equipment or system operates consistently
• Gives
reproducibility within defined specifications and parameters for prolonged
periods
Qualification
• Action
of proving and documenting that any premises, systems and equipment
• Properly
installed, and/or work correctly and lead to the expected results
• Qualification
is often a part (the initial stage) of validation
• Individual
qualification steps alone do not constitute process validation
Standard Operating Procedure (SOP)
• An
authorized written procedure giving instructions for performing operations
• Not
necessarily specific to a given product or material but of a more general
nature
• e.g.
equipment operation, maintenance and cleaning; validation
• Cleaning
of premises and environmental control
• Sampling
and inspection
Validation
• Action
of proving and documenting that any process, procedure or method
• Actually
and consistently leads to the expected results
Validation protocol (or plan) (VP)
• A
document describing the activities to be performed in a validation
• Including
the acceptance criteria for the approval of a manufacturing process or a part thereof — for routine use
Validation report (VR)
• A
document in which the records, results and evaluation of a completed
• Validation
program me are assembled and summarized
• It may also contain proposals for the
improvement of processes and/or equipment
Validation master plan (VMP)
• The
VMP is a high-level document that establishes an umbrella validation plan for
the entire project
• Summarizes the manufacturer’s overall
philosophy and approach
• To
be used for establishing performance adequacy
• It
provides information on the manufacturer’s validation work program
• Defines
details of and timescales for the validation work to be performed
• Including
a statement of the responsibilities of those implementing the plan
• Introduction
methodology
• Qualification
• Installation qualification
• Operational qualification
• Process qualification
• Personnel
• Schedule
• Preventive
maintenance
• Charge
control
• Procedures
• Documentation
• Appendixes
Verification
• The
application of methods, procedures, tests and other evaluations
• In
addition to monitoring, to determine compliance with the GMP principles
Worst Case
• A
condition or set of conditions encompassing the upper and lower processing
• Limits
for operating parameters and circumstances, within SOPs, which pose
• The
greatest chance of product or process failure when compared to ideal conditions
• Such
conditions do not necessarily include product or process failure
Encapsulation speed-
The formulation should be encapsulated at a wide range of
speeds to determine the operating range of the encapsulator
Summary
• Validation is a key process for
effective quality assurance
• Validation checks the accuracy and
reliability of a system or a process to meet the predetermined criteria
• Different types of validation are prospective
validation , retrospective validation , concurrent validation and revalidation
• The
VMP is a high-level document that establishes an umbrella validation plan for
the entire project
REFERENCE-
• http//www.pharmainfo.net/reviews/guidelines-general-principles-validation-solid-dosage.
• www.google.com