Quality by Design (QbD) is a systematic, scientific approach to pharmaceutical development and manufacturing that begins with predefined quality objectives. It focuses on understanding sources of variability in order to develop robust manufacturing processes and identifies critical quality attributes and control mechanisms. This proactive approach can help reduce FDA review time and queries compared to traditional methods that rely on end-product testing. However, fully implementing QbD requires overcoming challenges such as lack of expertise and resources as well as organizational resistance to change.
Bioanalytical Method Development and Validation..
Bioanalytical method validation include all the procedure that demonstrate that a particular method used for quantitative measurement of analyte in given biological matrix are reliable and reproducible for intended use.
Bioanalytical Method Development and Validation..
Bioanalytical method validation include all the procedure that demonstrate that a particular method used for quantitative measurement of analyte in given biological matrix are reliable and reproducible for intended use.
Overview of analytical method validationprarkash_dra
Validation is an important feature in any method of measurement because it is closely related to the quality of the results. A method of analysis is characterized by its performance parameters, which have to be assessed if they are to provide the correct performance values. These performance values must be in accordance with previously defined requirements that the method of analysis should satisfy. But above all, the performance parameters depend on the type of method and its intrinsic characteristics. So depending on what is needed, the user must choose which method of analysis will best solve the analytical problem.
Validation of Analytical and Bioanalytical methodssarikakkadam
Guidelines for Validation of Analytical and Bioanalytical methods as per ICH (Q2R1) and USFDA respectively with an example of Bioanalytical method validation.
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
When analytical method is utilized to generate results about the characteristics of drug related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods are fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy which documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of drug, production and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.
Global Regulatory Issues: one BA method, one validation, one report ...Peter van Amsterdam
Comparison of the recent guidelines of the Brazilian, European, Japanese and US regualtory agencies on bioanalytical method validation in order to be able to validate a bioanalytical method in such a way that it would meet the requirements of these 4 agencies. Presented at the 2013 Land O'Lakes meeting
Method validation for drug substances and drug product _remodified_2014Ramalingam Badmanaban
Method validation is the process of proving that an analytical method is acceptable for its intended purposes.
METHOD VALIDATION = ERROR ASSESSMENT
Method validation is the process of demonstrating that analytical procedures are suitable for their intended use and that they support the identity, strength, quality, purity and potency of the drug substances and drug products
Validation: Prior ConsiderationsSuitability of Instrument Status of Qualification and Calibration Suitability of Materials Status of Reference Standards, Reagents, Placebo Lots Suitability of Analyst Status of Training and Qualification Records Suitability of Documentation Written and approved standard test procedure and proper approved protocol with pre-established acceptance criteria
Compendial vs. Non-compendial Methods
Compendial methods-Verification
Regulatory analytical procedure in USP/NF
Non- compendial methods-Validation
Alternative analytical procedure proposed by the applicant for use instead of the regulatory analytical procedure
Chromatographic Methods
Demonstrate Resolution
Impurities/Degradants Available
Spike with impurities/degradants
Show resolution and a lack of interference
Impurities/Degradants Not Available
Stress SamplesFor assay, Stressed and Unstressed Samples should be compared.
Ability of an analytical method to measure the analyte free from interference due to other components.
Selectivity describes the ability of an analytical method to differentiate various substances in a sample
Original term used in USP
Also Preferred by IUPAC and AOAC
Also used to characterize chromatographic columns
Degree of Bias (Used in USP)
The difference in assay results between the two groups
the sample containing added impurities, degradation products, related chemical compounds, placebo ingredients
Selectivity: For impurity test, impurity profiles should be compared.
Temperature (50-60℃)
Humidity (70-80%)
Acid Hydrolysis (0.1 N HCl)
Base Hydrolysis (0.1 N NaOH)
Oxidation (3-30%)
Light (UV/Vis/Fl)
Intent is to create 10 to 30 % Degradation
Change in the analytical procedure, drug substance, drug product, the changes, may necessitate revalidation of the analytical procedures.
“The degree of revalidation depends on the nature of the change.”
“FDA intends to provide guidance in the future on post-approval changes in analytical procedures.”
By Visual Inspection of plot of signals vs. analyte concentration
By Appropriate statistical methods
Linear Regression (y = mx + b)
Correlation Coefficient, y-intercept (b), slope (m)
Acceptance criteria: Linear regression r2 > 0.999
Requires a minimum of 6 concentration levels
Normally derived from Linearity studies.
Established by confirming that the method provides acceptable degree of linearity, accuracy, and precision.
Specific range dependent upon intended application of the procedure.
What is Validation?
Methods validation is the process of demonstrating that analytical procedures are suitable for their intended use-Guidance for Industry
Validation is a process-risk will determine the effort
High Risk:Total validation
Moderate Risk:Testing,Documentation
Low Risk:Testing the change
Accuracy
ICH defines accuracy of an analytical procedure as the closeness of agreement between the conventional true value or an accepted reference value and the value found.
% Accuracy = Experimental- True Value * 100
True Value
Precision
Precision of analytical procedure is defined as closeness of agreement in values between a series of measurements. As per ICH, precision is considered at three different levels:
Repeatability or intra—assay precision: precision data are obtained by repeatedly analyzing, in one lab on one day, aliquots of a homogeneous sample.
Intermediate precision: precision obtained when the assay is performed by multiple analysts, multiple instruments, and multiple days in one lab.
Reproducibility: precision between laboratories.
Specificity
Specificity is the ability of the method to accurately measure the analyte response in the presence of all potential sample components.
It is very important in the analysis of complex mixtures by GC, HPLC, AA, ICP, etc.
Limit of Detection (LOD)
Limit of Detection (LOD) is the lowest amount of analyte in a sample which can be reliably detected but not necessarily accurately or precisely measured.
Signal/Noise = 2 to 3
Limit of Quantitation (LOQ)
Limit of Quantitation (LOQ) is the lowest amount of an analyte that can be quantitatively determined with suitable precision and accuracy.
Signal/Noise = 10 to 20
Linearity and Range
Linearity of an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample.
Range: Interval from the upper to the 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
Must cover 80-120% of product claims
Usually evaluated from the same data set as linearity, precision, accuracy
Want to learn more about analytical method validation, FDA requirements and best practices to comply with them? ComplianceOnline webinars and seminars are a great training resource. Check out the following links:
ICH, FDA and USP Requirements for Method Validation
How to Validate Analytical Methods and Procedures
Validation of Analytical Methods and Procedures
Eliminate the Confusion - Analytical Method Qualification and Validation
Lifecycle Approach to Analytical Methods with QbD Elements
Analytical Instrument Qualification and System Validation
Lifecycle Approach to Analytical Methods for Drug Products
For details vis
Pharmaceutical Quality by Design (QBD) is a concept introduced by the International Conference on Harmonization (ICH) Q8 guideline, as a systematic approach to development that begins with predetermined objectives and emphasizes the understanding of production and processes and process control, based on sound science and quality risk management.
The basic concept of QBD is “The Quality cannot be tested into the product, but it should be built into it.”
Overview of analytical method validationprarkash_dra
Validation is an important feature in any method of measurement because it is closely related to the quality of the results. A method of analysis is characterized by its performance parameters, which have to be assessed if they are to provide the correct performance values. These performance values must be in accordance with previously defined requirements that the method of analysis should satisfy. But above all, the performance parameters depend on the type of method and its intrinsic characteristics. So depending on what is needed, the user must choose which method of analysis will best solve the analytical problem.
Validation of Analytical and Bioanalytical methodssarikakkadam
Guidelines for Validation of Analytical and Bioanalytical methods as per ICH (Q2R1) and USFDA respectively with an example of Bioanalytical method validation.
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
When analytical method is utilized to generate results about the characteristics of drug related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods are fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy which documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of drug, production and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.
Global Regulatory Issues: one BA method, one validation, one report ...Peter van Amsterdam
Comparison of the recent guidelines of the Brazilian, European, Japanese and US regualtory agencies on bioanalytical method validation in order to be able to validate a bioanalytical method in such a way that it would meet the requirements of these 4 agencies. Presented at the 2013 Land O'Lakes meeting
Method validation for drug substances and drug product _remodified_2014Ramalingam Badmanaban
Method validation is the process of proving that an analytical method is acceptable for its intended purposes.
METHOD VALIDATION = ERROR ASSESSMENT
Method validation is the process of demonstrating that analytical procedures are suitable for their intended use and that they support the identity, strength, quality, purity and potency of the drug substances and drug products
Validation: Prior ConsiderationsSuitability of Instrument Status of Qualification and Calibration Suitability of Materials Status of Reference Standards, Reagents, Placebo Lots Suitability of Analyst Status of Training and Qualification Records Suitability of Documentation Written and approved standard test procedure and proper approved protocol with pre-established acceptance criteria
Compendial vs. Non-compendial Methods
Compendial methods-Verification
Regulatory analytical procedure in USP/NF
Non- compendial methods-Validation
Alternative analytical procedure proposed by the applicant for use instead of the regulatory analytical procedure
Chromatographic Methods
Demonstrate Resolution
Impurities/Degradants Available
Spike with impurities/degradants
Show resolution and a lack of interference
Impurities/Degradants Not Available
Stress SamplesFor assay, Stressed and Unstressed Samples should be compared.
Ability of an analytical method to measure the analyte free from interference due to other components.
Selectivity describes the ability of an analytical method to differentiate various substances in a sample
Original term used in USP
Also Preferred by IUPAC and AOAC
Also used to characterize chromatographic columns
Degree of Bias (Used in USP)
The difference in assay results between the two groups
the sample containing added impurities, degradation products, related chemical compounds, placebo ingredients
Selectivity: For impurity test, impurity profiles should be compared.
Temperature (50-60℃)
Humidity (70-80%)
Acid Hydrolysis (0.1 N HCl)
Base Hydrolysis (0.1 N NaOH)
Oxidation (3-30%)
Light (UV/Vis/Fl)
Intent is to create 10 to 30 % Degradation
Change in the analytical procedure, drug substance, drug product, the changes, may necessitate revalidation of the analytical procedures.
“The degree of revalidation depends on the nature of the change.”
“FDA intends to provide guidance in the future on post-approval changes in analytical procedures.”
By Visual Inspection of plot of signals vs. analyte concentration
By Appropriate statistical methods
Linear Regression (y = mx + b)
Correlation Coefficient, y-intercept (b), slope (m)
Acceptance criteria: Linear regression r2 > 0.999
Requires a minimum of 6 concentration levels
Normally derived from Linearity studies.
Established by confirming that the method provides acceptable degree of linearity, accuracy, and precision.
Specific range dependent upon intended application of the procedure.
What is Validation?
Methods validation is the process of demonstrating that analytical procedures are suitable for their intended use-Guidance for Industry
Validation is a process-risk will determine the effort
High Risk:Total validation
Moderate Risk:Testing,Documentation
Low Risk:Testing the change
Accuracy
ICH defines accuracy of an analytical procedure as the closeness of agreement between the conventional true value or an accepted reference value and the value found.
% Accuracy = Experimental- True Value * 100
True Value
Precision
Precision of analytical procedure is defined as closeness of agreement in values between a series of measurements. As per ICH, precision is considered at three different levels:
Repeatability or intra—assay precision: precision data are obtained by repeatedly analyzing, in one lab on one day, aliquots of a homogeneous sample.
Intermediate precision: precision obtained when the assay is performed by multiple analysts, multiple instruments, and multiple days in one lab.
Reproducibility: precision between laboratories.
Specificity
Specificity is the ability of the method to accurately measure the analyte response in the presence of all potential sample components.
It is very important in the analysis of complex mixtures by GC, HPLC, AA, ICP, etc.
Limit of Detection (LOD)
Limit of Detection (LOD) is the lowest amount of analyte in a sample which can be reliably detected but not necessarily accurately or precisely measured.
Signal/Noise = 2 to 3
Limit of Quantitation (LOQ)
Limit of Quantitation (LOQ) is the lowest amount of an analyte that can be quantitatively determined with suitable precision and accuracy.
Signal/Noise = 10 to 20
Linearity and Range
Linearity of an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample.
Range: Interval from the upper to the 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
Must cover 80-120% of product claims
Usually evaluated from the same data set as linearity, precision, accuracy
Want to learn more about analytical method validation, FDA requirements and best practices to comply with them? ComplianceOnline webinars and seminars are a great training resource. Check out the following links:
ICH, FDA and USP Requirements for Method Validation
How to Validate Analytical Methods and Procedures
Validation of Analytical Methods and Procedures
Eliminate the Confusion - Analytical Method Qualification and Validation
Lifecycle Approach to Analytical Methods with QbD Elements
Analytical Instrument Qualification and System Validation
Lifecycle Approach to Analytical Methods for Drug Products
For details vis
Pharmaceutical Quality by Design (QBD) is a concept introduced by the International Conference on Harmonization (ICH) Q8 guideline, as a systematic approach to development that begins with predetermined objectives and emphasizes the understanding of production and processes and process control, based on sound science and quality risk management.
The basic concept of QBD is “The Quality cannot be tested into the product, but it should be built into it.”
A presentation covering QbD inclusive of its definition, goals, advantages, QTTP, Risk Assessment Methods, Design of experiment, Life Cycle Management, etc.,
QbD is new concept in pharmaceutical industries which is beneficial for producing and maintaining quality in product. With help of QbD a quality is built in product during manufacturing.
The pharmaceutical Quality by Design is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. Quality by Design is emerging to enhance the assurance of safe, effective drug supply to the consumer, and also offers promise to significantly improve manufacturing quality performance
QbD can be applied to the development and evaluation of analytical methods. During
method development, all potential factors (the inputs) and all critical analytical
responses (the outputs) are studied to determine the relationships. Critical analytical
factors are identified in an approach that parallels what is described for process
development in ICH Q8 and Q9. A corporate knowledge repository is required
throughout the process to ensure critical information is captured that can be reviewed
and added to in the future such that lessons learned can be applied to the specific
methods under consideration and also to other similar methods being applied to other
products. s
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
2. The conventional development process uses an empirical
approach that requires continuous end product testing and
inspection to determine quality. The processes that create the
end product are seen as fixed, opposed to change, and focus
only on process reproducibility. This approach ignores real-
world variability in materials and process controls. There is a
different path. It’s called Quality by Design (QbD). With QbD
you will get a proactive approach to product development,
potential to reduce FDA queries and review time, and the
scientific data to quickly get to the root cause and resolution
of any deviation
2
3. Quality by Design (QbD) is a modern, scientific approach that
formalizes product design, automates manual testing, and
streamlines troubleshooting.
Definition :
The pharmaceutical Quality by Design (QbD) is a systematic
approach to development that begins with predefined
objectives and important product and process understanding
and process control, based on sound science and quality risk
management.
Quality by Design (QbD) is emerging to enhance the
assurance of safe, effective drug supply to the consumer, and
also offers promise to significantly improve manufacturing
quality performance.
3
4. Defining the Product Design Goal:
In this step, you define the Quality Target Product Profile (QTPP) and
identify all the critical quality attributes (CQA) for the product
Discovering the Process Design Space:
Understanding your processes is the key to defining the design space
Understanding the Control Space:
Based on the process design space, a well-executed control space can
be defined
Targeting the Operating Space:
The operating space is the best set of parameters, determined
statistically, which enable you to accommodate any natural variability
in CPPs and CQAs .
4
5. Proper implementation of QbD can potentially provide
three main benefits for development:
More efficient use of development time and costs.
Ability to meet FDA submission guidelines and
expectations.
Reduced approval times – and fewer queries – from
the FDA.
5
6. Insufficient understanding of the process and its
benefits.
Organizational resistance to change.
Denial of the need (“Our process is under control”).
Competing priorities.
Lack of resources and expertise in QbD .
6
8. Risk Assessment Report(s)
• Performed throughout QbD Process
• Particularly important to process development.
Quality Target Product Profile (QTPP)
• Defines the desired product characteristics and sets development goals.
Control Strategy Summary
• Defines the process, its inputs and outputs, and how it is controlled.
PPQ Report(s)
• Formal verification that the process Control Strategy has been defined
appropriately and repeatedly produces the desired results.
Continued Process Verification (CPV) Reports
• Assuring that during routine commercial production, the process remains in a
state of control (FDA); involves feedback loops into the QbD “process” where
intentional process changes and/or observed variability is assessed for risk,
characterized, re-validated, etc
8
9. Necessary Elements:
• Quality characteristics: sterility, purity etc. (including
specific safety-related impurities where necessary)
• Pharmacokinetic characteristics: dissolution etc.
• Therapeutic effect
• Target patient population: neonate, adult etc., clinical
diagnosis
• Shelf life: temperature, light conditions etc.
9
10. Critical Quality Attribute (ICH Q8):
“A property or characteristic that when controlled within
a defined limit, range, or distribution ensures the
desired product quality.”
• Potential CQAs are derived from the QTPP and guide
product and process development.
• CQAs are identified by quality risk management and
experimentation to determine the effect of variation on
product quality.
10
11. Many CS elements are developed via risk assessments:
• CQA/CPP, Raw Material, Components, Specifications
A CS is the final outcome of process development
(“Process Design” if using FDA terminology).
A CS is not a “point-in-time” activity, but rather should
evolve as knowledge increases.
A CS is constituted of many parts, many of which are
developed/written at different points in time throughout
process development.
11
12. Verification that the defined CS consistently delivers
the desired product quality
• PPQ is a significant product milestone
• Provides proof the process is well controlled
Establishes an initial baseline for future process
evaluation.
PPQ is a dynamic part of the validation concept
12
13. Continuous Improvement is the last component of the
QbD Process
CPV provides the “feedback” loop in the control of our
processes
Process Monitoring and Evaluation.
Other components of Continuous Improvement include
good integration of process knowledge into change
control, deviation management, etc.
13