Calibration &

Validation

Yashwanth A M

Assistant Professor

Dept of Pharmaceutics
 Calibration
Definition
Calibration is defined as the process of determining the accuracy of an instrument.

Calibration Involves:

(a) Obtaining a particular reading 1

from the instrument under study.

2 (b) Comparing this reading with one

obtained from a standard
instrument.
(c) Assessing the degree of variation 3
between the two readings.

4 (d) Adjusting the instrument so that

it gives readings in keeping with
established standards.
Objectives of Calibration
1 Accurate Readings
Calibration ensures that instruments provide accurate readings, minimizing errors and
discrepancies in measurements. This is crucial for maintaining product quality and
consistency.

2 Measurement Precision
Calibration determines the precision of instruments, assessing their ability to produce
consistent readings. This is essential for ensuring reproducible results and reliable data
analysis.

3 Reliability Assessment
Calibration helps evaluate the overall reliability of instruments, including their stability and
ability to maintain accuracy over time. This ensures that instruments remain trustworthy for
consistent performance.

4 Drift Detection
Calibration helps detect any drift or changes in an instrument's accuracy over time. This
allows for timely adjustments or replacements to prevent measurement errors.
Significance of Calibration
Equipment Degradation Environmental Influence Quality Assurance

Regular use of instruments can Ambient conditions like humidity, Regular calibration ensures the
lead to wear and tear, resulting in temperature, and pressure can continued accuracy and reliability
shifts in their accuracy. impact instrument of instruments, contributing to
Calibration helps track these measurements. Calibration helps the consistent quality of
shifts and provides data to rectify ensure that these factors do not pharmaceutical products and
instrument functioning. cause unacceptable deviations. meeting regulatory requirements.
Frequency of Calibration
Initial Installation 1
Instruments should be calibrated upon
installation before their first use.
2 Critical Measurements
Calibration should be performed both before
and after taking measurements critical to
Unusual Events 3 product quality.
Calibration is necessary after any event that
might have affected the instrument's
accuracy, such as a fall, impact, or electrical 4 Suspect Readings
shock. If readings appear inaccurate or questionable,
calibration should be conducted to verify the
Post-Repair 5 instrument's performance.
Instruments should be calibrated after any
repairs to ensure they function correctly.
6 Routine Schedule
A routine calibration schedule should be
established based on the instrument's type
Manufacturer Recommendations 7 and usage frequency.
Calibration should be performed at the
frequency recommended by the instrument
manufacturer.
 Consequences of Neglecting Calibration
Faulty Measurements
Neglecting calibration can lead to inaccurate measurements, which may affect product quality and consistency.

Safety Concerns
Inaccurate measurements can lead to variations in drug formulations, potentially affecting the safety and
effectiveness of the medication.

Waste of Resources
Faulty measurements may result in wasted resources due to product rejections, rework, or batch failures.

Production Delays
Issues arising from inaccurate measurements may lead to production delays as investigations, re-calibration, and
rework are required.

Product Recalls
In extreme cases, neglecting calibration can result in product recalls due to quality issues, potentially damaging a
company's reputation.
Calibration Methods
Method Description Applications

Standard Calibration Simple calibration using Instruments not critical to

traceable standards, quality or not required for
suitable for non-critical accreditation/licensing.
instruments.
Calibration with Data Similar to accredited Instruments requiring
calibration, but without calibration but not subject
data on measurement to strict ISO standards.
uncertainties.

ISO 17025 Accredited Strictest method, requiring Instruments critical to

Calibration a measurement report with quality, requiring
'as found' and 'as left' data compliance with ISO 17025
and a certificate. standards.
 Validation

Definition of Validation

"Validation is documented evidence that the process, operated

within established parameters, can perform effectively and
reproducibly to produce a Medicinal product meeting its
predetermined specifications and quality attributes’’
Scope of Validation in Pharmaceuticals

1 Equipment Validation 2 Facility and Utility 3 Process Validation

Validation
Ensuring the accuracy, Verifying that the
reliability, and suitability of Validating the design, manufacturing process
equipment for intended use. construction, and operation consistently produces a
of facilities and supporting product meeting quality
utilities (e.g., water systems, specifications.
air handling units).

4 Cleaning Validation 5 Analytical Method Validation

Demonstrating that cleaning procedures Establishing the accuracy, precision, and
effectively remove residues and prevent cross- reliability of analytical methods used to test raw
contamination. materials, intermediates, and finished products.
Advantages of Validation

Assured Quality Reduced Costs Increased Output Improved

Compliance
Validation ensures that By minimizing Validated processes are
products consistently production errors, typically more efficient, Validation helps
meet predefined quality rework, and rejections, leading to higher companies comply with
standards, enhancing validation helps reduce production output and regulatory requirements
patient safety and costs associated with faster time-to-market. and demonstrate
efficacy. maintaining quality. adherence to good
manufacturing practices.
Types of Validation
Major Types of Validation

Process validation Cleaning validation

Equipment validation Validation of analytical

methods
Process Validation
1 Definition:
As per FDA, Process validation is defined as, 'The
collection of data from the process design stage
throughout production, which establishes
scientific evidence that a process is capable of
consistently delivering quality products.
Objectives of Process
Validation
1 Reduce Batch Variation
Process validation helps to minimize batch-to-batch variation
and ensure consistent product quality.

2 Ensure Reproducibility
The validation process demonstrates the manufacturing
operation can be consistently reproduced.

3 Improve Efficiency
Process validation can lead to reduced testing, faster
investigations, and easier scale-up and maintenance.
Process validation - protocol

1 Objective and Scope 8 Critical quality attributes.

2 Validation team and Responsibility 9 Sampling and Testing Plan and

validation methodology.

3 List of Equipment 10 Acceptance Criteria

4 Batch Details subjected for validation. 11 Abbreviations

5 Manufacturing Process in Brief 12 Stability Study Requirement

6 Process Flow Diagram 13 Deviation, OOS and Recommendation.

7 Critical process parameters. 14 Summary and Conclusion

 Benefits of Process Validation
1 Reduction in utility cost.
5 Easier scale-up from development work

2 Reduced testing in-process and finished goods.

6 Easier maintenance of equipment.

3 More rapid and accurate investigations

7 Improved awareness of processes.
into process deviation.

4 More rapid and reliable start-up of new

8 Rapid automation.
equipment
Types of Process validation
1 Prospective validation 2 Retrospective validation

3 Concurrent validation 4 Revalidation

Prospective Validation
Definition Purpose Application

Validation conducted before the To demonstrate that the process Used when a new process is
will consistently produce a
process is put into commercial being introduced or when
product meeting its
use predetermined specifications significant changes are made to
and quality attributes. an existing process.
Concurrent Validation
Definition Purpose Application

Validation conducted during To confirm that the process is in Often used when a limited
control during routine production
actual production, usually for a number of batches are
process that has already been produced, and prospective
validated prospectively validation is not feasible
Retrospective Validation
Definition Purpose Application

Validation based on the review To confirm that an existing Applied to processes that have
process is consistently
and analysis of historical data been in use for some time,
producing a product that meets
from previously completed all its specifications. particularly those for which
production batches extensive historical data is
available
 Revalidation
Definition
Re-validation provides evidence that changes in a process
and/or the process environment that are introduced do not
adversely affect process characteristics and product quality.

Purpose
To confirm that changes or modifications have not
affected the process's ability to produce a quality product.

Application
Used after any significant changes to equipment,
process parameters, or raw materials, or after a certain
number of batches have been produced
Cleaning Validation
1 Definition
Cleaning validation is the documented evidence that the
cleaning process consistently removes residues (cleans)
to an acceptable level, preventing cross-contamination.

2 Objectives
The key objectives of cleaning validation are to minimize
cross-contamination, determine the efficiency of the
cleaning process, and troubleshoot any issues.

Application
3
Applied to cleaning processes for equipment, utensils,
and surfaces that come into contact with
pharmaceutical products.
 Equipment Validation (Qualification)
Equipment validation is termed as
Phases of Qualification
There are four major phases of qualification
Qualification

Design Qualification (DQ)

Definition: Validation of equipment Verifies the equipment design meets the user requirements and regulatory standards.
to ensure it operates correctly and
produces the desired results.
Installation Qualification (IQ)
Confirms the equipment is properly installed and meets the design specifications.

Purpose: To ensure equipment is

properly installed, operates as Operational Qualification (OQ)
intended, and performs Demonstrates the equipment operates within the predetermined parameters.
consistently within specified
limits.
Performance Qualification (PQ)
Verifies the equipment consistently performs as intended under routine operating conditions.

Other phases include URS, FAT, and SAT

I. User requirement specification (URS)
User Department Equipment/Instrument Technical Specifications
Information Details
Capacity or Sensitivity, Mode of
Name of the User department Name of the Equipment / Construction, Documentation
with Location. Instrument. Purpose of the (Qualification and Operation
Equipment / Instrument. Manuals), List of Components or
Spares etc.

Critical Control Points Supporting Utilities

Details of the Critical Control Points including the Supporting Utilities available like AHU, Water, Steam
software information. or Electricity etc.,

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II. Design Qualification
1 Purpose 2 Timing
Design qualification demonstrates if the proposed design of the Wherever appropriate, design qualification (DQ) of the equipment
equipment is suitable for intended purpose. The shall be carried out before accepting the equipment for installation.
equipment/system then shall be subjected to order.

3 Installation 4 Verification
The equipment/system/ facility shall be installed with support of The design of equipment shall be visually verified and cross-
vendor at its designated location. All the required utilities shall be checked physically, if in case of absence of documentary evidence.
identified and supported to the equipment/system/ facility.
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II. Design Qualification
5 Design Review 6 Documentation Review

Where appropriate, a review of the developed design shall be done to ensure The above requirements are ensured through documented review of following

that cGMP compliance has been addressed at the design stage: ✓ the documentation, where appropriate: ✓ Supplier manual ✓ Technical

Compliance with CGMP requirement. ✓ Practical validation tests are possible. document

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Design Qualification Protocol:
✓Approval of the Protocol ✓Objective ✓Scope

✓Acceptance Criteria and Responsibilities ✓URS ✓Equipment Description

✓Technical Design Specification of Equipment ✓Functional Design Specification ✓Major Components/Accessories: All critical
variables and its MOC with respect to equipment,
area or system under qualification to be mentioned

✓Supporting utilities required ✓Cabling/power details ✓MOC and Finishing of all Components

✓P and I Drawings ✓Critical Control Parameters ✓Safety features

✓Appendix (Reference Documents)

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III. Factory Acceptance Test (FAT)

1 Machine Construction
After completion of the construction of machine, inspection of machine at the factory site as per DQ shall be carried out by user / client. This inspection before delivery to the user site is called FAT.

2 FAT Protocol Preparation

Manufacturer of the machine will prepare the FAT protocol based on the DQ, as built machine specifications, calibration certificates, documents of spares and equipments mounted on machine, then this FAT protocol will be sent to
client/user for review and approval.

3 User Review and Approval

User will review and approve the FAT protocol. The user / client will visit the factory of machine manufacturer to inspect the readiness for delivery of the machine as per FAT protocol.

4 FAT Execution
FAT is generally first stage of system testing and should be witnessed by the customer prior to agreement for the machine to be delivered to the user site. The manufacturer should ensure that machine can pass the predefined test prior
to the witnessed acceptance testing so as to minimize the risk of failing in any testing.

5 FAT Verification
During the FAT, user should test and verify every component of machine for operation and functioning as per predefined acceptance criteria. User will also verify as built drawing with machine, calibration of the instruments, documents of
calibrations, other calibration and MOC certificates. Check the safety controls, signals and critical control points as per DQ. Perform the functional test as per requirement and FAT protocol.

6 FAT Outcome
If the machine complies the URS, DQ and Acceptance Criteria, it is recommended for the delivery to the site.

7 FAT Documentation
The FAT protocol and report shall be reviewed and approved by manufacturer and user after completion of FAT and before delivery of the machine. • If the machine does not complies with the acceptance criteria, modifications shall be
approved through the change control system. Re FAT shall be carried out in case of modifications.

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IV. Site Acceptance Test (SAT)
Machine Inspection Machine Receipt Verification of Components
SAT is the process of inspection with documentation Once the machine has been delivered to the user site, it Spares parts, tools need to be checked as per the
of the machine at the user site for any change, will be received by the user as per SOP of receipt of the packing list as well as documents such as manuals
damage, ware and tare during the transit before the machines and equipment’s. The manufacturer will sent and calibration certificates etc. also need to be
installation of the machine. the engineering team for the installation of the verified.
machine at the user site. Machine will be removed out
from the packaging in front of Engineering team, will be
inspected for any damage during the transit.

SAT Protocol Site Verification SAT Outcome

SAT protocol will be prepared by the machine Machine manufacturer will also check and verify the Observations and results should be recorded and if the
manufacturer and will be reviewed by both site for machine installation such as temperature, machine complies SAT specification and acceptance
manufacturer and user before implementation. humidity, flooring, power supply, service lines etc., if it criteria then only the machine is recommended for IQ.
is not as per the requirement of the machine, machine
manufacturer can ask to rectify the things before the
SAT and IQ.

SAT Documentation
The SAT protocol and report is reviewed and approved by manufacturer and user after the completion of the SAT and before the Installation Qualification.

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V. Installation Qualification (IQ)

Purpose
IQ demonstrates that the facility, equipment, control system, utilities and selected components are installed as per the approved design and at the specified locations. Required SOP's, operating manuals are available and all the critical
measuring devices are calibrated using an established calibration program.

Verification
IQ is documented verification that all key aspects of the equipment, instrument or ancillary systems have been properly selected and constructed, that they are installed in accordance with the design requirements and established
specifications.

IQ Protocol
The IQ protocol shall define the responsibilities, procedures, documentation, references, acceptance criteria, deviation and requalification criteria to be used in the installation of the equipment/system.

System Description
The IQ protocol shall contain a description of the system, including a discussion of intended use and major components.

Static Attributes Verification

The execution of the protocol verifies the system's static attributes against the user and manufacturer's specifications prior to normal operation. The system shall be examined for proper connection and installation of supporting services
for example, compressed air and electricity etc. Model, serial numbers and equipment identification numbers of equipment and major subsystems of each piece of equipment is recorded. Material of construction shall verify for product
contact surfaces. Drawings are checked during IQ execution.

Documentation Verification
Critical supporting documentation, such as manufacturer's manuals, vendor test results, purchase orders, specifications, drawings and any other required documentation are verified as available and the file locations noted. All instruments
are identified during IQ and calibration completed prior to the start of OQ.

SOP Identification
Standard Operating Procedures (SOP) for Operation, Preventative Maintenance and Cleaning shall be identified.
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Installation Qualification (IQ) Protocol:

Protocol Approval Scope System Description Other process equipment

attached

Execution team Equipment/ System Test Procedures Evaluation of Test Data

Qualification

If any Discrepancy then Reference documents

corrective action report

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VI. Operational Qualifications (OQ)

1 Purpose 2 Execution 3 Protocol Definition

Operational Qualification (OQ) is documented After the successful completion of the IQ, the Test objectives, methodologies and
evidence establishing confidence that the OQ protocol is executed. The OQ describes acceptance criteria shall be defined in the
equipment, instrument or ancillary systems operational tests and measurements of key preapproved OQ.
operate as intended and are capable of parameters critical for the proper operation of
consistent operation within established the system.
specifications.

4 Personnel Training 5 Variance Management 6 Change Control

As part of the OQ process, Operator and Variances encountered during the OQ are Any change(s) made to the system/equipment
Maintenance Personnel training should be identified. Appropriate corrective actions are during the OQ must be documented in the OQ
done and documented in the protocol. taken to allow validation to proceed. report. Any changes proposed after the OQ
(during performance qualification or routine
manufacturing) must be managed through the
Change Control system in accordance with the
Change Control SOP.

7 OQ Summary Report
A summary report is written at the completion of OQ for review and approval before proceeding to PQ or PV, as applicable.
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Operational Qualification (OQ) Protocol:

✓Introduction Objective ✓SOP Reference

✓Responsibilities ✓Test Functions

✓Data Sheets ✓Corrective Action Report

Data sheets: for checks against it acceptance criteria If any Discrepancy then corrective action report.
and make observations and signatures.

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VII. Performance Qualification (PQ)

1 Purpose 2 Prerequisites
Performance Qualification (PQ) is documented evidence that the equipment, The PQ shall not proceed without completion of the IQ/OQ execution. The
instrument or ancillary systems, when operating in its environment and PQ integrates procedures, personnel, materials, utilities, equipment and
under stress scenarios perform as intended in meeting predetermined supporting controls, as necessary.
specifications.

3 Test Design 4 Replicate Studies

Test objectives, methodologies and acceptance criteria are defined and Where appropriate, a sufficient number of replicate studies are performed to
approved prior to execution. determine the ability of the equipment and supporting controls to achieve
reproducible results.

5 Utility Testing 6 Variance Management

Utility testing may include capacity and quality measurements under actual Any variance encountered during the PQ is identified for review. Exceptional
operating conditions. The protocol may incorporate load challenges to the conditions are investigated and the appropriate corrective actions shall
intended operating range of the equipment/supporting controls. taken.

7 Documentation 8 Verification
PQ summary report is written at the competition at PQ for review and PQ can be verified in the process validation document and whenever
approval. required, PQ can be performed separately.
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PQ Protocol Sections
✓ Objective ✓ Scope

✓ Critical variables to be met: ✓ Documents to be attached:

All critical variables with Relevant documents like
respect to equipment, area or validation reports,
system under qualification to performance reports etc., to
be mentioned. be attached.

✓ Any changes made against ✓ Review (Inclusive of follow

the formally agreed design up action, if any)
parameters.

✓ Recommendation ✓ Approval

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Requalification
When any equipment undergoes any kind of modification or
relocation on a scale that has a direct impact on the product quality,
it must undergo a re-qualification. This process must be handled
with a documented change control procedure, after due review and
authorization.

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Validation of the
Analytical Method /
Analytical Method
Validation Definition
Analytical method validation is the process of proving that an
analytical method is acceptable for its intended purpose.

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General Principles and Parameters
of Analytical Method Validation
1 Suitable Protocol and Procedures
The most suitable analytical validation protocol and procedures should be chosen for
testing of their product by manufacturer and the chosen procedure should be demonstrated
(through validation) to be suitable for its intended purpose.

2 Validation for All Methods

All analytical methods irrespective of stability indicating method need to be validated.

3 Validation During Development

The analytical method should be validated by research and development team during
product development.

4 Common Analytical Procedures

Most common analytical procedures include identification tests, assay of drug substances
and pharmaceutical products, quantitative tests for content of impurities and limit tests for
impurities. Other analytical procedures include dissolution testing and determination of
particle size.
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 General Principles and Parameters of
Analytical Method Validation
Accuracy
5
Analytical results using stated analytical procedures should be accurate, precise, reliable and
reproducible.

6 Pharmacopoeial Methods
When Pharmacopoeial methods are used for analysis, proper evidence needs to be generated
to suitability of method for routine use in the laboratory.

7 Specificity of Pharmacopoeial Methods

Pharmacopoeial methods used for the analysis of impurities pharmaceutical products should
be checked for its specificity (no placebo interference)

8 Validation of Non-pharmacopoeial Methods

In case of Non-pharmacopoeial methods, all such methods should be appropriately validated.

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Method Validation
Protocol Development
Analytical method validation should be conducted in accordance with
preapproved protocol which includes analytical procedures and acceptance
criteria for the results.

Validation Report
Validation report should be prepared after conducting validation activities.

Justification for Non-Pharmacopoeial Methods

If the Pharmacopoeial method is available for the non-pharmacopoeial method in
use then proper justification of the method used need to be provided by
comparing results with Pharmacopoeial method available.

Documentation
Standard test methods should be documented to provide sufficient information
to allow properly trained analysts to perform the analysis in a reliable manner

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Method Verification
1 Purpose
Method verification also called as partial validation and is performed for already validated
analytical methods in following cases.

2 Case 1
(a) When an already validated method is used on a product for the first time For example in case
of a change in active pharmaceutical ingredient (API) supplier, change in the method of
synthesis or after reformulation of a drug product;

3 Case 2
(b) When an already validated method is used for the first time in a laboratory. Method
verification may include only the validation characteristics of relevance to the particular change.

4 Example
For example, in the case of a change in API supplier, the only expected difference would be in
the impurity profile or solubility of the API, and therefore, for a related substances method, there
should be an appropriate verification that the method is able to detect and quantitate all
potential ssimpurities, even the late eluting ones. Specificity also can be considered for
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Method Revalidation
1 Maintenance of Validation 2 Trigger for Revalidation
Validated state of analytical methods should remain over the life Revalidation of an analytical procedure should be considered
of the method whenever there are changes made to the method.

3 Examples of Changes 4 Periodic Revalidation

For example: changes to the mobile phase, changes to the Periodic revalidation also needs to be considered with a
temperature of the column; changes to the predefined frequency.
concentration/composition of the sample and standards;
changes to the detector etc.
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Characteristics of Analytical Procedures

1 Accuracy

2 Precision

3 Robustness

4 Linearity

5 Range

6 Specificity

7 Detection limit

8 Quantitation limit
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1. Accuracy
1 Definition
As per WHO, Accuracy is the degree of agreement of test
results with the true value, or the closeness of the results
obtained by the procedure to the true value.

2 Establishment
It is normally established on samples of the material to be
examined that have been prepared to quantitative accuracy.

3 Range
Accuracy should be established across the specified range
of the analytical procedure.

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2. Precision
Definition
Precision is the degree of agreement among individual results.

Measurement
The complete procedure should be applied repeatedly to separate, identical samples drawn from the same homogeneous batch of material. It should be measured by
the scatter of individual results from the mean (good grouping) and expressed as the relative standard deviation (RSD).

1 Repeatability
Repeatability should be assessed using a minimum of nine determinations covering the specified range for the procedure, e.g. three concentrations/three replicates
each or a minimum of six determinations at 100% of the test concentration.

2 Intermediate Precision
It expresses within-laboratory variations (usually on different days, different analysts and different equipment). If reproducibility is assessed, a measure of intermediate
precision is not required

3 Reproducibility
expresses precision between laboratories.
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3. Robustness (or ruggedness)

1 Definition 2 Influence 3 Development Phase

It is the ability of the procedure The results from separate Robustness should be
to provide analytical results of samples are influenced by considered during the
acceptable accuracy and changes in the operational or development phase and
precision under a variety of environmental conditions. reliability of an analysis when
conditions. deliberate variations are made
in method parameters.

4 Verification of Stability 5 Liquid Chromatography

The verification of the stability of analytical solutions In the case of liquid chromatography, robustness
is of particular importance. Other characteristics of testing may also include verification of the impact of
robustness include extraction time. changes in pH, temperature and flow rate.

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Factors Affecting Robustness
in Chromatographic Analysis
Stability of test and standard samples and solutions

Reagents (e.g. different suppliers)

Different columns (e.g. different lots and/or suppliers)

Extraction time

Variations of pH of a mobile phase

Variations in mobile phase composition

Temperature

Flow rate

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4. Linearity
1 Definition
It indicates the ability to produce results that are directly
proportional to the concentration of the analyte in samples.

2 Sample Preparation
A series of samples should be prepared in which the analyte
concentrations span the claimed range of the procedure.

3 Statistical Evaluation
If there is a linear relationship, test results should be
evaluated by appropriate statistical methods. A minimum of
five concentrations should be used.
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Range
Range
The range is an expression of the lowest and highest levels of
analyte that have been demonstrated to be determinable for the
product.

Specified Range
The specified range is normally derived from linearity studies.

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Specificity
Specificity
Specificity (selectivity) is the ability to measure unequivocally
the desired analyte in the presence of components such as
excipients and impurities that may also be expected to be
present.

Investigation of Specificity
An investigation of specificity should be conducted during the
validation of identification tests, the determination of impurities
and assay.

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Detection Limit
The detection limit (limit of detection) is the smallest quantity of an
analyte that can be detected, and not necessarily determined, in a
quantitative fashion.

Approaches may include instrumental or non-instrumental

procedures and could include those based on:

✓ visual evaluation;

✓ signal to noise ratio;

✓ the standard deviation of the response and the slope;

✓ standard deviation of the blank;

✓ calibration curve.
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Quantitation Limit
Quantitation limit (limit of quantitation) is the lowest concentration of
an analyte in a sample that may be determined with acceptable
accuracy and precision.

Approaches may include instrumental or non-instrumental

procedures and could include those based on:

✓ visual evaluation;

✓ signal to noise ratio;

✓ the standard deviation of the response and the slope;

✓ standard deviation of the blank;

✓ calibration curve
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VALIDATION MASTER
PLAN
Definition
A Validation Master Plan (VMP) is defined as the document that
provides information about the company's validation
programme. This document must contain details of validation to
be done, and the timeframes for the studies to be performed.

VMP Details
There must be clear statements regarding who is responsible for
each part of the validation program.

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Purpose of VALIDATION MASTER
PLAN
1 Comprehensive Overview
The main purpose of the VMP is to give a comprehensive overview of the complete
operation, how it has been organized, what all it will cover, and the validation plan.

2 Management Understanding
It helps to management to understand how much time will be required, personnel to be
involved, and expenses expected to be incurred.

3 Team Information
It informs members of the validation team about their jobs and responsibilities.

4 Inspector/Auditor Understanding
It helps inspectors/auditors to understand the company's approach to validation
activities.

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Who should write the VMP?
1 Team Writing Effort
• From team writing effort – members from all department.

2 Diverse Perspectives
• When people from diverse areas of the operation are involved, it is
more likely that all possible angles of approaching the VMP are
covered.

3 Comprehensive Information
• A VMP must be as lengthy as required to convey all the necessary
information to ensure a successful validation program.

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Elements of a Good VMP
Validation Policy Organizational Structure Summary of Facilities,
A clear and concise statement outlining Defines the roles and responsibilities of
Systems, Equipment, and
the company's commitment to validation individuals and departments involved in
Processes
and its principles. validation activities. A comprehensive list of all validated and
to-be-validated aspects of the
manufacturing process.

Documentation Format Planning and Scheduling Change Control

Specifies the format and content of Outlines the timeline and resources Defines procedures for managing
validation protocols and reports. allocated for validation activities. changes to validated processes and
systems.

References to Existing Documents

Includes relevant guidelines and standards that inform the VMP.
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Guidelines for Preparing VMP
1 Clear and Legible Style
The VMP should be written in a clear and concise manner, preferably on
A4 size paper.

2 Explanatory Drawings and Figures

Include sufficient drawings, figures, and flow charts to illustrate the
validation process.

3 Clear Division of Validation Types

The VMP should be clearly divided into different validation types without
any overlap.

4 Proper Dating and Authorization

The VMP must be dated and signed by authorized personnel.
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Qualification and Validation Protocols
Objectives of the Study

Site of the Study

Responsible Personnel

Type of Validation

Description or Reference of SOPs

Equipment to be Used

Standards and Acceptance Criteria

Processes and/or Parameters

Sampling, Testing, and Monitoring Requirements

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Qualification and Validation Reports

1 Written Reports 2 Report Content

Written reports should be available for all qualification Reports should include the title, objectives, protocol
and validation activities. reference, materials, equipment, procedures, and test
methods.

3 Evaluation of Results 4 Deviation Management

Results should be evaluated based on the protocol and Deviations or out-of-specification results should be
compared to acceptance criteria. investigated, justified, and addressed.

5 Report Approval 6 Conclusion

Reports should be approved by the responsible The report should conclude with a statement about the
departments and the quality assurance department. success or failure of the qualification or validation.

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Contents of a VMP
Title Page Table of Contents Glossary Plan for Validation

Includes document Lists out critical areas of Defines technical terms Details the process steps,
number, version the VMP. and abbreviations. critical parts of the
information, and approval process, and what is to
signatures. be validated.

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Contents of a VMP (Continued)
Management's Scope of Validation Roles and Outsourced
Approach to Responsibilities Services
Validation
Defines what will be Specifies the roles and Details any services to be
Outlines the company's covered under validation responsibilities of outsourced to external
overall approach to and what will not be different departments vendors.
validation. covered. involved in validation.

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Contents of a VMP (Continued)
Change Control Risk Management Training of Validation Matrix
Procedures Policy Personnel
Outlines the validation
Defines procedures for Outlines the company's Specifies the training required throughout the
managing changes to approach to identifying, requirements for manufacturing facility,
validated processes and assessing, and mitigating personnel involved in from most to least
systems. risks. validation activities. critical.

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Calibration of pH Meter
Two-Point Calibration Method
Uses two buffers of known pH (pH 7.0 and either pH 4.01 or pH 9.20) to calibrate the pH meter.

Temperature Considerations
Ensure that all buffers are at the same temperature before calibration, as pH can vary with temperature.

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Calibration Procedure

Step 1: Warm-up 1
Switch on the pH meter and allow it to warm up according to
the instrument's operating manual.
2 Step 2: Electrode Preparation
Remove the electrode from its storage solution, rinse with
distilled water, and blot dry with tissue paper.
Step 3: Calibration with pH 7.0 Buffer 3
Place the electrode in pH 7.0 buffer, press the "Measure" or
"Calibrate" button, and adjust the calibration button to read
7.0 if necessary. 4 Step 4: Calibration with Acidic or Alkaline
Buffer
Place the electrode in either pH 4.01 or pH 9.20 buffer, press

Step 5: Electrode Cleaning and Storage 5

the "Measure" or "Calibrate" button, and adjust the
calibration button to read the corresponding pH value.
Remove the electrode from the buffer, clean with distilled
water, blot dry, and return to the storage solution.

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Qualification of UV-
Visible
Spectrophotometer
The UV-Visible spectrophotometer is an instrument that is used to
measure absorbance of solutions over the ultraviolet and visible
ranges of the electromagnetic spectrum, generally between 200 -
800 nanometres

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Qualification Steps
Qualification of the UV-Visible spectrophotometer involves the following steps:

1 Design Qualification
The type and make of the instrument to be purchased must be
chosen carefully depending on the specific requirements of the type
of samples that will need to be measured.

2 Installation Qualification
(a) Install the instrument in a room that is maintained at temperature
between 15-25°C and relative humidity of 45 - 80%. (b) The
installation site must be away from dust, corrosive liquids or gases
and direct sunlight. (c) Remove the instrument from its packing
material, and place it on a surface that does not vibrate. (d) Install the
computer near the instrument, or load the software into an existing
computer.

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(d) Check the following parameters at this
stage:

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Operational Qualification

(a) Connect the instrument to the mains and switch it on.

(b) Follow the operating manual instructions and check for the
following parameters: Wavelength accuracy, linearity of
absorbance, resolution, wavelength reproducibility, photometric
accuracy, stray light, photometric noise, baseline flatness and
photometric stability.

(c) Measure the values obtained for each of the above parameters
and check if they meet the specified acceptance criteria. Record
these values.
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Performance Qualification
(a) Define the performance criteria that are most important to routine operations.

Parameter Specification Acceptance Criteria Measured Value

Appearance Intact, no defects visible Must be present ✓

Operational manual Provided Must be present ✓

Parts All parts present as per Must be present ✓

operating manual

Hardware and software Supplied Must be present ✓

(b) Define the acceptance criteria for these performance criteria selected. Parameters Specification Appearance Intact, no defects visible Operational
manual provided Must be present Parts All parts present as per operating manual Hardware and software supplied Must be present

(c) Determine the values for the chosen criteria and check if they meet the acceptance limits set.

(d) Decide on the frequency of regular calibration and performance qualification for routine use of the instrument.
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