3. DEFINITION
Validation means rectification or confirmation.
Validation can be defined as a procedure that demonstrates that a process under
standard conditions is capable of consistently producing a product that meets the
established product specifications.
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5. 1) ANALYTICAL METHOD VALIDATION
Method validation must prove that the analytical method used for a specific test is
suitable for which it is to be carried out.
►Methods should be validated when:-
● When they are to be established for routine use.
● When the method is to be changed due to change in conditions.
● Whenever the equivalence between new method and the standard are
demonstrated
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6. TYPES OF PROCEDURES TO BE VALIDATED
1) ACCURACY:-
The accuracy of an analytical method refers to the closeness of agreement between the observed
value and the value which is either conventially a true one or reference one.
► 2) PRECISION:-
The precision of an analytical method refers to the closeness of values obtained from a series of tests.
► 3) REPEATABILITY:-
Repeatability is established when the same sample is estimated repeatedly by the same analyst using
same analytical method within the same laboratory using same instrument and performed within
a short period of time.
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7. ► 4) INTERMEDIATE PRECISION:-
When the test is repeated on different days by different persons or using different instruments within
the same laboratory,the variation is expressed in terms of intermediate precision.
► 5) REPRODUCIBILITY:-
When a method is standardized,the test is carried out in different laboratories using the same
method,the precision between the laboratories is refered to as reproducibility.
► 6) SPECIFICITY:-
Specificity is the ability of a test method to measure the analyte explicity in the presence of other
components.
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8. 7) LINEARITY:-
● Linearity of an analytical method refers to it’s ability to measure a specific component within
a range.
► 8) DETECTION LIMIT
► 9) QUANTITATION LIMIT
► 10) ROBUSTNESS
► 11) RANGE
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9. 2) EQUIPMENT VALIDATION
Equipment validation is to provide a high level of documented evidence that the equipment and the process
confirm to a standard.
TYPES
(a) INSTALLATION QUALIFICATION (IQ)
(b) OPERATIONAL QUALIFICATION (OQ)
(c) DESIGN QUALIFICATION (DQ)
(d) PERFORMANCE QUALIFICATION (PQ)
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10. It ensures that all major processing and packing equipment and ancillary systems
are in conformity with installation specification,equipment manuals ,schematics
►Important IQ considerations:-
● Calibration,preventive maintenance
● Safety features
● Software documentation
● Equipment design features
(a) INSTALLATION QUALIFICATION (IQ)
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11. It is done to provide a high degree of assurance that the equipment functions as intended.
It is conducted in 2 stages- component operational qualification & system operational
qualification.
Important OQ considerations:-
● Software procedures
● Raw material specification
● Process operation procedures
● Material handling requirements
(b) OPERATIONAL QUALIFICATION (OQ)
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12. It is a documented review of the design, at an appropriate stage in the project, for
conformance to operational and regulatory expectation.
►Important DQ considerations are:-
● GMP’s and regulatory requirements
● Reliability and efficiency
● Safety and environment impact
● Construct ability and installation of equipment
(c) DESIGN QUALIFICATION (DQ)
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13. It is a documented verification that all aspects of a facility, utility or equipment
perform as intended in meeting pre-determined acceptance criteria.
►Important PQ considerations:-
● Actual product & process parameters
● Acceptability of the product
● Process repeatability
● Long term process stability
(d) PERFORMANCE QUALIFICATION(PQ)
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14. 3) CLEANING VALIDATION
Cleaning validation ensures that there is no cross contamination in a multi-product manufacturing
plant and also prevents microbial contamination
► Once a product is manufactured,the equipment is cleaned using appropriate cleaning SOP’S
established during IQ of the equipment
► TYPES OF CONTAMINATION TO BE CONSIDERED IN CLEANING VALIDATION
● Cross contamination
● Microbial contamination
● Contamination by cleaning or sanitizing agent
● Contamination by other agents
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15. 4) PROCESS VALIDATION
Process validation is the means of ensuring & providing documentary evidence that processes are capable of
repeatedly & reliably producing a finished product of the required quality.
TYPES
(a) PROSPECTIVE VALIDATION
(b) CONCURRENT VALIDATION
(c) RETROSPECTIVE VALIDATION
(d) PROCESS RE-VALIDATION
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16. It is conducted prior to the distribution of either a new product or a product made under a modified
production process, where the modifications are significant & may affect the product characteristics.
► It includes:-
● Initial stages of formulation devolepment & process devolepment
● Setting of process sampling plans
● Designing of batch records
● Defining raw material specifications
● Transfer of technology from scale up to commercial size batches
● Environmental controls
(a) PROSPECTIVE VALIDATION
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17. Here, the validation protocol is executed before the process is put into
commercial use.
It is generally considered acceptable that three consecutive batches within
the finally agreed parameters,giving product of the desired quality would
constitute a proper validation of the process.
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18. It is a process where current production batches are used to monitor processing parameters.
It gives of the present batch being studied, and offers limited assurance regarding consistency of
quality from batch to batch.
Examples of these may be when:-
● A previous validated process is being transferred to a third party contract manufacturer or to
another site
(b) CONCURRENT VALIDATION
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19. ● The number of batches produced are limited
● Process with low production volume per batch and market demand
● The product is a different strength of a previously validated product with the same
ratio of active or inactive ingredients
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20. It is conducted for a product already being marketed and is based on extensive
data accumulated over several lots and over time.
►This validation may be used for older products which were not validated by the
fabricator at the time that they were first marketed.
►Retrospective validation is only acceptable for well established detailed processes
and will be inappropriate when there have recent changes in the formulation of the
products,operating procedures,equipment & facility.
(c) RETROSPECTIVE VALIDATION
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21. Some of the essential elements of this validation are:-
● Batches manufactured for a definite period
● Number of lots released per year
● Master manufacturing/packaging documents
● List of process deviations,corrective actions & changes to manufacturing documents
● Data for stability testing for several batches
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22. Process re-validation is required when there is a change in any of the critical process
parameters ,formulation,primary packaging components,major equipmenta or premises
► Examples when process re-validation is required when:-
● Changes in raw materials ( physical properties such as density,viscosity,particle size
distribution)
● Changes in source of active raw material manufacturer
(d) PROCESS RE-VALIDATION
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23. ● Changes in packaging material ( primary container/ closure system)
● Changes in the process (Mixing time,drying temperatures & batch size)
● Changes in the equipment
● Changes in the plant/facility
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24. REFERENCE
Industrial pharmacy , A Comprehensive approach, by D.K Tripathi,
Pg no: 671-699
►Pharmaceutical process validation : An overview , by M.d Shoaib Alam
etal;Journal of advanced pharmacy education & research ,oct-dec
2012,vol 2, issue 4, pg no: 190-196
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