ICH Q14 Guideline Overview_SS_AI.pptx.pdf

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1. ICH Q14 GUIDELINE
OVERVIEW
1
Understanding the New Guideline for
Analytical Procedure Development
By: Mr. PANKAJ GAWATE
https://www.linkedin.com/in/pankaj-gawate-722b9887/
Cont.: 8454845526
Mail ID: [email protected]

2. 21. Introduction to ICH Q14
❑ICH Q14 describes Science and risk-based
approaches for developing and maintaining analytical
procedures suitable for the evaluation of the quality
of drug substances and drug products.
❑It also includes additional considerations for the
development of multivariate analytical procedures
and for real time release testing (RTRT).
❑This guideline includes augmenting ICH Q2’s
validation principles.
❑It incorporates methods from ICH Q8 and Q9,
offering traditional and enhanced developmental
approaches.

3. 2. Objective & scope 3
OBJECTIVE: The objective of this guideline is to produce
‘fit for purpose’ analytical methodology with the requisite
specificity, accuracy and precision over the method’s intended
range. This is principally aimed at the ongoing development
and lifecycle management of established methods of
commercial products and is aligned with ICH Q12.
SCOPE: This guideline covers new or revised analytical
procedures for testing commercial drug substances and
products, applicable to both chemical and biological types.
It may extend to various product types with regulatory
consultation, but doesn’t include developing pharmacopeial
procedures.

4. 4
3. General Considerations for
Analytical Procedure Development and
Lifecycle Management
❑This section outlines strategies for developing analytical
procedures with high specificity, accuracy and precision,
using minimal and enhanced approaches.
❑Existing procedures may be adopted to new products,
simplifying development and reducing validation tests.
Development data, like robustness from design of
experiments (DOE) can also serve as validation data
guidedbyICHQ2.
❑Using tools from ICH Q12, the guideline details principles
for change management of analytical procedures based on
risk management and understanding of performance
characteristics.

5. • Identification of the attributes of the product which need to be tested
• Selection of an appropriate technology and related instruments or suitable apparatus
• Conduct studies to evaluate analytical procedure performance characteristics such as specificity, accuracy
and precision over the reportable range (including the calibration model, lower and/or higher range limits) and
robustness;
• Documenting the analytical procedure including the analytical procedure control strategy
Enhanced approach:
• Conducting risk assessment and evaluating prior knowledge to identify the analytical procedure parameters
that can impact performance of the procedure;
• Conducting uni- or multi-variate experiments and/or modelling to explore ranges and interactions between
identified analytical procedure parameters;
• Defining an analytical procedure control strategy including set-points and/or ranges for relevant analytical
procedure parameters. These could include proven acceptable ranges for analytical procedures (PARs) and/or
method operable design regions (MODRs).
5
Minimal approach:
3.1 Minimal vs enhanced approaches

6. 63.2 The analytical procedure lifecycle

7. 7
Knowledge and risk
management in
Analytical procedure
development and
continual
improvement
Discover
Capture
Process
Benefit &
Share
Simple diagrammatic representation of analytical procedure lifecycle

8. 4. Analytical Target Profile 8
1) Product and Process Understanding
oICH Q8 and ICH Q11 frameworks guide the identification of critical quality attributes (CQAs) essential for
analytical measurement and control.
2) Quality Target Product Profile (QTPP)
oCQAs identified can be included in the QTPP, which outlines the quality expectations for drug products.
3) Analytical Target Profile (ATP)
oAn ATP outlines the intended purpose of the analytical procedure and details product attributes to be measured
alongwith performance characteristics.
4) Measurement Requirements
oThe ATP specifies measurement needs for one or more quality attributes, guiding the development of analytical
procedures.
TheATPdefinestheintendedpurpose,thespecificproductattributestobemeasured and the performance
requirementsforthoseattributes. Byestablishingthesecriteria,theATPensuresthat analytical methods are
scientificallysound,risk- based,andcapableof consistently evaluating the quality of drug substances and products.
This approach facilitates acceptance and supports effective change management throughout the products lifecycle.
Different steps are:

9. ANALYTICAL TARGET PROFILE CONT… 9
5) Choice of Analytical Technology
The ATP influences the selection of analytical technology, considering multiple techniques that can meet
performance criteria.
6) Operating Environment Consideration
The choice of analytical technology also factors in the operating environment, whether at-line, in-line, or off-line.
Newdrug'sdissolutionrate.Theanalyticaltargetprofile(ATP)forthismethodwouldoutlinethecritical
attributes,suchasthespecificdissolutionratetobemeasured,theacceptablerangeofvariability,andthe
requiredsensitivityandprecisionofthemeasurement.Itmightstatethatthemethodshouldaccuratelyquantify
thepercentageofthedrugdissolvedatspecifictimepointswithaprecisionof±2%.Byestablishingthesecriteria
upfront,theATPGuidesthemethoddevelopmentprocess,ensuringtheanalyticalprocedureconsistentlymeets
thequalityrequirementsandregulatoryexpectationsthroughoutthedrug'slifecycle.

10. 5. Knowledge and risk management in analytical
procedure development and continual improvement
10
1.KnowledgeManagement:
❑Establisharobustknowledgemanagementsystemtocaptureandshareinformationonanalytical
procedures.
❑Ensurethatallrelevantdata,includinghistoricaldata,isaccessibleandusedto
informmethoddevelopmentandvalidation.
2.RiskManagement:
❑Implementarisk- basedapproachtoidentifyandmitigatepotentialrisksassociated
withanalyticalprocedures.
❑Conductriskassessmentsatvariousstagesofmethoddevelopmenttoensurethe
reliabilityandrobustnessofthemethods.
3.ContinualImprovement:
❑Continuouslymonitorandevaluatetheperformanceofanalyticalproceduresto
identifyareasforimprovement.
❑Implementcorrectiveandpreventiveactionsbasedontheevaluationresultsto
enhancethequalityandefficiencyofanalyticalmethods.

11. 6. Evaluation of robustness and parameter ranges of
analytical procedures
11
1.Robustness:
❑Measurestheabilityofananalyticalproceduretoremainunaffectedbysmall,deliberatevariationsinmethod
parameters.
❑Conductedduringmethoddevelopmenttoensurethemethodperformsconsistentlyundernormalusage
conditions.
2.ParameterRanges:
❑Definestheacceptablelimitsforcriticalmethodparameters(e.g.,temperature,pH,flowrate).
❑Establishestherangewithinwhichthemethodcanproducereliableandaccurateresults.
Byevaluatingrobustnessandparameterranges,ICHQ14ensuresthatanalyticalproceduresarereliable,consistent,
andcapableofmaintainingperformanceunderexpectedvariations.

12. 7. Analytical procedure control strategy 12
•Developacontrolstrategythatensurestheanalyticalprocedureremainsreliableandconsistent
throughoutitslifecycle.
•Incorporateriskmanagementprinciplestoidentifyandmitigatepotentialsourcesofvariability.
ControlStrategy
Design:
•Implementcontrolmeasuressuchassystemsuitabilitytests,calibration,andmaintenanceof
equipment.
•Establishacceptancecriteriaforeachcontrolmeasuretoensureongoingmethodperformance.
Control
Measures:
•Continuouslymonitortheperformanceoftheanalyticalprocedurethroughregularsystemsuitabili
tychecksandperformancequalification.
•Reviewcontroldatatoidentifytrendsordeviationsthatmayindicateaneedforcorrectiveactions
.
Monitoringand
Review:
•Defineproceduresforinvestigatingandaddressingdeviationsfromcontrolcriteria.
•Implementcorrectiveactionstorestoremethodperformanceandpreventrecurrenceofissues.
Corrective
Actions:

13. 8. Lifecycle management and post-approval changes of
analytical procedures
13
Arisk-basedapproachforidentifyingEstablishedConditions(ECs)anddefiningreportingcategoriesfor
associatedchangesiscrucial. 1) Including analytical procedure control strategy 2) In some cases, moderate risk
changes proposed by the company may require prior approval based on health authority feedback
Figure 2: Risk-based approach for identification of ECs and reporting categories for associated changes in the enhanced approach

14. Examples of analytical procedure change evaluation
14
For product and process changes, a
reassessment and potential adaptation of the
ATP, and a reassessment of the suitability of
the analytical procedure is necessary. If an
applicant proposes a new analytical
procedure, a comprehensive risk assessment
and evaluation should be conducted to
determine any impact on the performance.

15. 159. Development of multivariate analytical
procedures : additional considerations
DEFINITION OF MULTIVARIATE PROCEDURES:
Multivariate analytical procedures involve results determined
through calibration models utilizing multiple input variables.
Different steps are as follows:
Sample and sample population
Data transformation
Variable selection
Robustness
Recalibration and model maintenance

16. 16
The multivariate model lifecycle (Figure 3) is iterative and can be broken down into 3 major components: model establishment,
routine use and model maintenance.

17. 17
10. Development of analytical procedures for real time
release testing: additional considerations
•Definition of real-time release testing (RTRT):
RTRT evaluates and ensures product quality based on process data, including measured material
attributes and process controls.
Relationship to product control strategy: RTRT works with elements of the product control strategy,
such as process monitoring and in-process controls, to maintain quality.
•Application of RTRT: RTRT can be applied to drug substances, intermediates, and drug products using
specific process measurements and material attributes.
•Critical quality attributes (CQAs):
RTRT should focus on specific CQAs, with fully justified relationships to acceptance criteria.
•Validation of analytical procedures: RTRT analytical procedures must be validated as per ICH Q2,
ensuring process measurements have appropriate specificity for targeted quality attributes.
Quantitative results presentation: RTRT results should be expressed in the same units as traditional
testing to maintain clarity and consistency.

18. 11. Submission of analytical procedure related
information
18
1. Inclusion of Analytical Procedures
Analytical procedure descriptions must be included in ICH M4Q CTD sections 3.2.S.4.2 for drug substance and
3.2.P.5.2 for drug product.
2. Validation Data Submission
Validation data and supportive information justifying the analytical procedure control strategy should be submitted
in sections 3.2.S.4.3 and 3.2.P.5.3.
3. Detailing Analytical Procedures
The analytical procedure must be sufficiently detailed for skilled analysts to perform the analysis, including the
system suitability test (SST).
4. Guidance Compliance
Submission of validation data should align with ICH Q2 guidance, including performance criteria from the validation
study.
5. Development Data Justification
In certain cases, development data may be submitted as justification, particularly for techniques like dissolution
testing.
6. Differentiation of Ecs
When proposing enhanced characteristics (ECs) for analytical procedures, they must be clearly differentiated from
supportive information.
7. Lifecycle Management Considerations
If lifecycle management elements from ICH Q12 are included, the submission must adhere to principles described
in ICH Q12 and relevant chapters.

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8. Enhanced Approach Documentation
Justification for enhanced elements in the analytical procedure control strategy must be described in the dossier,
including performance characteristics.
9. Risk-Based Categorization
For proposed ECs and reporting categories, risk-based categorization should be included, with justification for
parameters classified as ECs.
10. Multivariate Analytical Procedures
Development information for multivariate analytical procedures must align with their impact level, as per ICH-
Endorsed Guide.
11. Validation Information for RTRT
Validation information for analytical procedures used for the release of drug substances or products, including
RTRT, should be included in the validation sections.
12. Description of Validation Approach
For multivariate models, the validation approach and results must include details like validation set description
and performance criteria evaluation.
13. RTRT Analytical Procedure Details
The analytical procedure for RTRT should cover attributes of interest, measurement principles, calibration data
acquisition, and model specifications.
14. Alternative Control Strategy Information
Sections 3.2.S.4.2 and 3.2.P.5.2 should also include descriptions of analytical procedures part of registered
alternative control strategies.

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•Method development: focus on understanding the purpose of the analytical method and its context in the
overall development process.
•Validation: outlines criteria for method validation, including specificity, accuracy, precision, linearity, range, and
robustness.
•Lifecycle management: encourages continuous evaluation and revalidation as part of the method lifecycle,
adapting to changes in processes or products.
•Documentation: stresses the need for comprehensive documentation to support method validation and
ongoing performance monitoring.
•This guideline aims to ensure that analytical methods are reliable, reproducible, and suitable for their intended
use throughout a product'slifecycle.

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