Validation

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:

  1. Gather
    the numerical data from the completed batch record and include assay
    values, end-product test results, and in-process data

  2. Organize
    these data in a chronological sequence according to batch manufacturing
    data, using a spreadsheet format

  3. Include
    data from at least the last 20–30 manufactured batches for analysis

  4. Trim
    the data by eliminating test results from noncritical processing steps and
    delete all gratuitous numerical information

  5. Subject
    the resultant data to statistical analysis and evaluation

  6. Draw
    conclusions as to the state of control of the manufacturing process based
    on the analysis of retrospective validation data.

  7. 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

 

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