VALIDATION

VALIDATION
Action of proving, in accordance with the principles of
Good Manufacturing Practice, that any procedure,
process, equipment, material, activity or system
actually and consistently leads to the expected results
(PIC/S,WHO)
PURPOSE OF VALIDATION
• Regulatory compliance
• Assurance of quality
• Process optimization
• Safety
• Reduction of quality costs
WHO IS RESPONSIBLE FOR
VALIDATION?
▪ Responsibility: Multi disciplinary
▪ Prime responsibility: Production and Quality Control
Departments
▪ Others involved: Engineering, R&D, contractors
The company must define the responsibilities of its
personnel and external contractors in the qualification
and validation program.
WHO IS RESPONSIBLE FOR
VALIDATION?
A pharmaceutical company should identify what
qualification and validation work is required to prove
that the critical aspects of their particular operation are
controlled.

The key elements of a qualification and validation

program should be clearly defined and documented in
a validation master plan.
VALIDATION TEAM
▪ General Manager
▪ Plant Manager
▪ Project Manager
▪ QA Manager
▪ GMP Manager
▪ Production Manager
▪ Validation Manager
▪ Engineering Manager
▪ R&D Manager
RESPONSIBILITIES OF THE
VALIDATION TEAM
▪ Identify needs
▪ Develop protocols
▪ Conduct the validation/qualification
▪ Assess the data generated
▪ Approve the equipment/system/process
SYSTEMS TO BE VALIDATED
• Equipment
• Facilities
• Utilities
• Manufacturing Processes
• Analytical Methods
• Software
• Cleaning
• Environment
• Materials
• Warehouse
• Controls
• Personnel
• Operating Procedures
VALIDATION MASTER
PLAN (VMP)
VALIDATION MASTER PLAN (VMP)
The VMP is a high-level document that establishes an
umbrella validation plan for the entire project and
summarizes the manufacturer’s overall philosophy,
intentions and approach to be used for establishing
performance adequacy.
VALIDATION MASTER PLAN (VMP)
Provides information on
▪ The manufacturer’s validation work program
▪ Details of the timescales for the validation work to be
performed
▪ Responsibilities of those implementing the plan
APPROACHES TO
VALIDATION
APPROACHES TO VALIDATION
1. Based on evidence obtained through testing
▪ Prospective Validation
▪ Concurrent Validation
2. Based on analysis of accumulated (historical) data
▪ Retrospective Validation
PROSPECTIVE VALIDATION
Establishing documented evidence that a process,
procedure, system, equipment or mechanism used in
manufacture does what it purports to do based on a
pre-planned validation protocol
CONCURRENT VALIDATION
Validation carried during routine production of
products intended for sale
RETROSPECTIVE VALIDATION
Validation of a process for a product that has been
marketed based upon accumulated manufacturing,
testing and control batch data on the condition that
composition, procedures and equipment remain
unchanged
VALIDATION PROTOCOL
VALIDATION PROTOCOL
A document describing the activities to be performed
in a validation activity, including the acceptance criteria
for the approval of a manufacturing process or a part
thereof for routine use
VALIDATION PROTOCOL
▪ Objectives of the study
▪ Site of the study
▪ Responsible personnel
▪ Description of SOPs to be followed
▪ Equipment to be used
VALIDATION PROTOCOL
▪ Standards and criteria for the relevant products and
processes
▪ Type of validation
▪ Processes and parameters
▪ Sampling, testing and monitoring requirements
▪ Predetermined acceptance criteria for drawing
conclusions
▪ Number of validation runs
VALIDATION PROTOCOL
▪ A protocol is a written set of instructions broader in
scope than a Standard Operating Procedure (SOP). SOPs
are the detailed written instructions for procedures
routinely performed in the course of any of the activities
associated with pharmaceutical manufacturing.

▪ A protocol describes the details of a comprehensive

planned study to investigate the consistent operation of
new system/equipment, a new procedure, or the
acceptability of a new process before it is implemented.
VALIDATION PROTOCOL
▪ Protocols include significant background information,
explain the rationale for and the objective of the
study, give a full description of the procedures to be
followed, set out the parameters to be measured,
describe how the results will be analyzed, and
provide pre-determined acceptance criteria for
making conclusions.
VALIDATION REPORT
▪ A document in which the records, results and
evaluation of a completed validation program are
assembled and summarized. It may also contain
proposals for the improvement of processes and/or
equipment.
ANALYTICAL METHOD
VALIDATION
EXAMPLE
ANALYTICAL METHOD VALIDATION
▪ Demonstrates that an analytical procedure is suitable
for its intended purpose
▪ The analytical method should be validated by
research and development before being transferred
to the quality control unit when appropriate.
ANALYTICAL PERFORMANCE
CHARACTERISTICS
Specificity
The ability to assess unequivocally the analyte in the
presence of components which may be expected to be
present

Linearity
The ability (within a given range) to obtain test results
which are directly proportional to the concentration
(amount) of analyte in the sample.
ANALYTICAL PERFORMANCE
CHARACTERISTICS
Range
The interval between the upper and lower concentration
(amounts) of analyte in the sample (including these
concentrations) for which it has been demonstrated that
the analytical procedure has a suitable level of precision,
accuracy and linearity
Accuracy/Trueness
Expresses the closeness of agreement between the value
which is accepted either as a conventional true value or an
accepted reference value and the value found
ANALYTICAL PERFORMANCE
CHARACTERISTICS
Precision
expresses the closeness of agreement (degree of scatter)
between a series of measurements obtained from multiple
sampling of the same homogeneous sample under the
prescribed conditions

Precision may be considered in three different levels:

1. REPEATABILITY/INTRA-ASSAY PRECISION
2. INTERMEDIATE PRECISION
3. REPRODUCIBILITY
ANALYTICAL PERFORMANCE
CHARACTERISTICS
1. Repeatability/Intra-assay precision
expresses the precision under the same operating
conditions over a short interval of time
2. Intermediate Precision
expresses within-laboratories variations: different days,
different analysts, different equipment, etc
3. Reproducibility
expresses the precision between laboratories (collaborative
studies, usually applied to standardization of methodology)
ANALYTICAL PERFORMANCE
CHARACTERISTICS
Detection Limit
The lowest amount of analyte in a sample which can be
detected but not necessarily quantitated as an exact value

Quantitation Limit
The lowest amount of analyte in a sample which can be
quantitatively determined with suitable precision and
accuracy
ANALYTICAL PERFORMANCE
CHARACTERISTICS
Robustness
A measure of the capacity to remain unaffected by small,
but deliberate variations in method parameters which
provides an indication of the reliability during normal
usage
System suitability testing
Tests based on the concept that the equipment,
electronics, analytical operations and samples to be
analyzed constitute an integral system that can be
evaluated as such
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