The document discusses applying a lifecycle management model to analytical procedures. It proposes a three stage model: 1) Procedure Design involving development and understanding potential variables, 2) Procedure Performance Qualification demonstrating fitness for purpose, and 3) Continued Procedure Performance Verification involving routine monitoring. Key aspects include defining an Analytical Target Profile specifying performance criteria, conducting risk assessments of potential variables, and establishing control strategies. The lifecycle approach aims to better integrate validation, transfer, and verification, with the Analytical Target Profile serving as an overall reference point.
Analytical method validation, ICH Q2 guidelineAbhishek Soni
Analytical Method Validation, ICH Q2 Guideline.
General principles related to the analytical method validation.
Validation of analytical method as per International Council for Harmonisation(ICH) guidelines and the United States Pharmacopeia(USP).
Glossary.
Useful in understanding the terms :
Specificity
Linearity
Range
Accuracy
Precision
Detection limit
Quantitation limit
Robustness
Ruggedness
System suitability testing
Analytical method validation, ICH Q2 guidelineAbhishek Soni
Analytical Method Validation, ICH Q2 Guideline.
General principles related to the analytical method validation.
Validation of analytical method as per International Council for Harmonisation(ICH) guidelines and the United States Pharmacopeia(USP).
Glossary.
Useful in understanding the terms :
Specificity
Linearity
Range
Accuracy
Precision
Detection limit
Quantitation limit
Robustness
Ruggedness
System suitability testing
Analytical Target Profile (ATP) - Structure and Application Throughout the An...pi
ICH Q2: Validation of Analytical Procedures describes the current concepts of validation, verification and transfer of procedures. This approach addresses portions of the analytical lifecycle but also has a number of downsides. As an alternative to this approach, predefined criteria can be established in the form of an Analytical Target Profile (ATP).
Understanding of Analytical Method Validation Approach in Pharmaceutical Industry. Analytical method validation Verification is a wide chapter and a huge scope of applicability. In different types of methods, instrument, measurement approach all can effect the validation effort. However the basic fundamental will remains same, the parameters, acceptance criteria, functionality may vary depending upon the type of method, instrument etc.
This document is intended to provide guidance for registration applications on the content and qualification of impurities in new drug substances produced by chemical syntheses and not previously registered in a region or member state.
Analytical Target Profile (ATP) - Structure and Application Throughout the An...pi
ICH Q2: Validation of Analytical Procedures describes the current concepts of validation, verification and transfer of procedures. This approach addresses portions of the analytical lifecycle but also has a number of downsides. As an alternative to this approach, predefined criteria can be established in the form of an Analytical Target Profile (ATP).
Understanding of Analytical Method Validation Approach in Pharmaceutical Industry. Analytical method validation Verification is a wide chapter and a huge scope of applicability. In different types of methods, instrument, measurement approach all can effect the validation effort. However the basic fundamental will remains same, the parameters, acceptance criteria, functionality may vary depending upon the type of method, instrument etc.
This document is intended to provide guidance for registration applications on the content and qualification of impurities in new drug substances produced by chemical syntheses and not previously registered in a region or member state.
Method validation is the process of documenting / proving that an analytical method provides analytical data acceptable for the intended use. A pharmaceutical drug product must meet all its specifications throughout its entire shelf-life. The performance of product characteristics throughout the shelf-life must be tested by analytical method for the product’s chemical, physiochemical, microbiological and biological characteristics. The method of analysis used must be validated. This is required to ensure the product’s safety and efficacy throughout all phases of its shelf-life. Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stages.
General Principles of Analytical Method of Validation.pdfTamannaKumari8
Validation is the process of establishing documentary evidence demonstrating that a procedure, process, activity carried out in
testing and then production maintain the desirable level of compliance all stages.
The process of providing the analytical procedure is acceptable or its intended us.(ICH Q
Analytical control strategy - Part -4 : How the ACS Applies to the Product Lifecycle and How the modern concept of a lifecycle model can be applied to analytical procedures.
5-Scientific Approach to Validation.pptxAllanThomas30
Validation is a Science and even the most mundane tasks in healthcare environments, like hand washing, must be validated (to ensure correct method and other factors like correct hand wash agent) and also verified - to create an acceptable baseline for post handwash counts.
Speaker at seminar "The Pharmaceutical quality system: ICH Q8/ICH Q9" - University of Parma, 18 May 2012.
Describing steps, tools, and approaches developed for application of QbD to manufacturing processes that have analogous application to the development and use of analytical methods.
Pharmaceutical Instrument and Analytical Validation and Qualification (SHOPNI...ShopnilAkash5
Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stages
It is essential to ensure the quality Of a product and Good Manufacturing Practices including all other regulatory requirements
NDSRIs - Nitrosamine Drug Substance-Related Impurities (NDSRIs)Chandra Prakash Singh
NDSRIs impurities share structural similarity to the API (having the API or API fragment in the chemical structure) and are therefore unique to each API.
NDSRIs generally form in the drug product through nitrosation of APIs (or API fragments) that have secondary or tertiary amines when exposed to nitrosating agents such as residual nitrites in excipients used to formulate the drug product.
Generally, the presence of high levels of NDSRIs has been associated with drug products rather than APIs because NDSRI formation usually results from a reaction between the API or API fragment and nitrosating agents in the drug formulation.
However, NDSRIs can potentially form in APIs when nitrosating agents are present in the API manufacturing process or when APIs undergo processing steps that can potentially induce their formation such as fluid bed drying at an elevated temperature and jet milling because these can create favorable conditions in which nitrogen oxides can react with at-risk APIs.
NDSRIs often lack carcinogenicity and mutagenicity study data (typically from animal studies) from which an AI limit can be determined.
This guidance provides a recommended methodology for AI limit determination that uses structural features of NDSRIs to generate a predicted carcinogenic potency categorization and corresponding recommended AI limit that manufacturers and applicants can apply, in the absence of other FDA recommended AI limits, in their evaluations of approved and marketed drug products as well as products in development or under review by FDA.
Currently Identified Risk Factors for Presence of Nitrosamines.pptxChandra Prakash Singh
N-Nitrosamines can be formed when an amine and nitrosating agent are combined under favourable conditions although other generation pathways are also possible, such as e.g. oxidation and reduction processes from hydrazine-type compounds and N-nitro derivatives.
Root causes for N-nitrosamines in medicinal products identified to date can be grouped as risk factors linked exclusively with the manufacturing process and storage of active substance and/or as risk factors associated with manufacture and storage of the finished product.
Moreover, there are risk factors specifically linked to GMP aspects.
Basic Understanding of LCMS
Ion Optics Path and Parameters.
Mass spectrometry measures the mass-to-charge ratio of ions to identify unknown compounds, to quantify known compounds, and to provide information about the structural and chemical properties of molecules.
The mass spectrometer has a series of quadrupole filters that transmit ions according to their mass-to-charge (m/z) ratio.
When the energy of the accelerated electrons is higher than a certain threshold value (which depends on the metal anode), a second type of spectrum is obtained superimposed on top of the white radiation. It is called the characteristic radiation and is composed of discrete peaks.
The energy (and wavelength) of the peaks depends solely on the metal used for the target and is due to the ejection of an electron from one of the inner electron shells of the metal atom.
This results in an electron from a higher atomic level dropping to the vacant level with the emission of an X-ray photon characterised by the difference in energy between the two levels.
CHARACTERIZATION OF CRYSTALLINE AND PARTIALLY CRYSTALLINE SOLIDS BY X-RAY POWDER DIFFRACTION (XRPD)
USP <941>
Every crystalline phase of a given substance produces a characteristic X-ray diffraction pattern.
Diffraction patterns can be obtained from a randomly oriented crystalline powder composed of crystallites (crystalline regions within a particle) or crystal fragments of finite size.
Essentially three types of information can be derived from a powder diffraction pattern:
The angular position of diffraction lines (depending on geometry and size of the unit cell).
The intensities of diffraction lines (depending mainly on atom type and arrangement and preferred orientation within the sample.
Diffraction line profiles (depending on instrumental resolution, crystallite size, strain, and specimen thickness).
LCMS - Ion Optics Path and Parameters
Source and gas parameters: These parameters can change depending on the ion source used.
Compound parameters: These parameters consist mostly of voltages in the ion path. Optimal values for compound-dependent parameters vary depending on the compound being analyzed.
Resolution parameters: These parameters affect the resolution and calibration.
Detector parameters: These parameters affect the detector.
A divert valve allows you to switch portions of the mobile phase to waste before the mass spectrometer.
This is particularly important for the portion containing all the un-retained components – many of which are likely to be involatile and contaminate the source. If you really want to keep things clean use a divert valve to divert everything to waste except the compounds of interest.
The integrated diverter valve, which is located next to the ion source, can be plumbed in injector mode or diverter mode.
LCMS Interface
API techniques (ESI, APCI and APPI)
In LCMS, ions can be generated through either the continuous or pulsed (discontinuous) modes.
The three API techniques (ESI, APCI and APPI) that were introduced operates in the continuous mode, giving a constant flow/supply of ions to the MS.
On the other hand, the pulsed mode generates a discontinuous source of ions such as the Matrix-Assisted Laser Desorption/Ionization (MALDI).
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.
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.
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
Safalta Digital marketing institute in Noida, provide complete applications that encompass a huge range of virtual advertising and marketing additives, which includes search engine optimization, virtual communication advertising, pay-per-click on marketing, content material advertising, internet analytics, and greater. These university courses are designed for students who possess a comprehensive understanding of virtual marketing strategies and attributes.Safalta Digital Marketing Institute in Noida is a first choice for young individuals or students who are looking to start their careers in the field of digital advertising. The institute gives specialized courses designed and certification.
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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.
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
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.
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
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
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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.
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June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...
Analytical procedures life cycle management
1. Lifecycle Management of
Analytical Procedures
How the modern concept of a lifecycle model can be applied to analytical procedures.
Chandra Prakash Singh
3. In alignment with process validation, three stages are proposed
Procedure Design
(Development and
understanding)
Procedure
Performance
Qualification
Continued Procedure
Performance Verification
A fundamental component of the lifecycle approach to analytical procedures is
having a predefined objective that stipulates the performance requirements for
the analytical procedure. These requirements are derived from the Analytical
Target Profile (ATP).
Lifecycle model
Process
validation
ICH guidelines Q8,
Q9, and Q10
Lifecycle Model
Any analytical procedure must be shown to be fit for its intended purpose before use.
The concept of QbD is understood as a “systematic approach that begins with
predefined objectives and emphasizes product and process understanding
and process control, based on sound science and quality risk management”.
4. Lifecycle Principles
Adoption of lifecycle
approach would
introduce new
concepts
The Analytical Target Profile and associated
predefined acceptance criteria.
Evaluation of the uncertainty associated with the
analytical procedure.
Incorporation of risk analysis strategies.
Consideration of the potential effect of changes to an
analytical procedure in the context of the analytical
procedure's lifecycle
5. Cornerstone concepts in
lifecycle management
The Analytical Target
Profile (ATP)
Risk management Control strategy
Knowledge
management
The Lifecycle Management
6. The Analytical Target Profile (ATP)
• The objective of the test and quality requirements, including the expected
level of confidence, for the reportable result that allows the correct conclusion
to be drawn regarding the attributes of the material that is being measured.
Defines
• The understanding of the target measurement uncertainty, which is the
maximum uncertainty that the data should have in order to maintain
acceptable levels of confidence in data quality.
Based on
• A reference point for assessing the fitness of an analytical procedure not only
in the development phase but also during all changes within the analytical
lifecycle.
Serves as
7. The Analytical Target Profile (ATP)
• The procedure must be able to accurately quantify [drug] in a range from [A units] to [B
units] in the [description of test article] in the presence of [x, y, z] with an accuracy =
100% ± [D%] and a precision ≤ [E%] for the reportable value.
Example 1:
• The procedure must be able to quantify [analyte] in a range from [A units] to [B units] in
the [description of test article] in the presence of [x, y, z] so that the distribution of the
total analytical error of the reportable value falls within the total allowable analytical
error range of ± [C%].
Example 2:
The second example species that the combined accuracy and precision, or the distribution
of the total analytical error (TAE), must fall within the desired level.
8. Risk Management
QRM for analytical procedures
Systematic process for the
• Assessment
• Control
• Communication
• Review of risks
To the quality of data across the
product lifecycle.
Identification of
Variables
The variables should
include all aspects of
the full analytical
procedure
Sampling
Sample preparation
Standards
Reagents
Facility
Equipment operating conditions.
9. The identified
variables
Should be evaluated using
appropriate risk-assessment tools
and prioritized experimentation
To understand,
eliminate, or mitigate
areas of risk.
Risk Management
CNX approach
C=Control,
N=Noise,
E=Experimental
A decision can be
made concerning
Which variables should be controlled (C)
Which are potential noise factors (N)
Which should be examined experimentally
(X)
To classify all
identified variables.
To determine
acceptable
ranges.
10. Risk Management
Risk-analysis and DOE
Risk-analysis tools can
be used to screen
experimental (X)
variables for DOE
studies to minimize the
total number of
experiments conducted
while maximizing
knowledge gained.
The results of DOE studies
provide justification of the
critical variables and their
acceptable ranges (from the risk
assessment and experimental
work), are inputs in the
Analytical Control Strategy, and
are explicitly specified in the
analytical procedure.
12. Quality risk
management,
control
strategy, and
knowledge
management:
how they work
together.
Identify as many variables as possible
(prior knowledge)
Assign risk based on potential impact
on data precision and accuracy
(risk identification).
The variables identified to have impact
on the data will be subject to DOE
(risk evaluation).
This leads to process understanding.
Based on the process understanding
risk control.
Risk reduction
Risk acceptance
Risk unacceptable
Risk review (routine monitoring)
Continuous
improvement
Deviations from ATP*
*(Unfavourable trend, Potentially result of a change in one or more variables).
Advantages of Adopting a Lifecycle Approach for Managing Analytical Procedures
Knowledgemanagement
Control
Strategy
Iterative
Risk Communication
13. Lifecycle
Stages
Stage 1: Procedure
Design
Procedure Development and Understanding
(Identify and Study Potential Analytical Variables)
Experimental Robustness Studies
Knowledge Gathering and Preparation
Stage 2: Procedure
Performance
Qualification
Stage 3: Continued
Procedure
Performance
Verification
Routine Monitoring
Observed Variations
Continual Improvement
Lifecycle Stages
In order to
provide a
holistic
approach to
controlling an
analytical
procedure
throughout its
lifecycle.
14. Common Variation and Special Variation
Upper Limit
Lower Limit
Unacceptable common
cause variation
Special cause
variation
Fit for purpose –
common cause variation
is acceptable and no
special cause variation
Observed Variations During the investigation, particular attention should be given to special cause variation
(shifts, drift, and deviation) and common cause variation (unacceptable noise).
15. Observed Variations
Variation may
result when a
particular
procedure variable
is not adequately
controlled. This
variation may arise
for a number of
reasons:
A variable was not identified or adequately studied during the procedure
understanding study (Stage 1), and therefore no proper control was defined.
A variable was not identified or adequately studied during Stage 2 (precision
study), and therefore no proper control was defined.
Series member of a set of categorical variables (not included in the DoE, Stage 1)
has been found to have an effect on performance (e.g., a new batch of column
packing results in unacceptable performance).
A control strategy was defined but not followed.
A noise variable has been found to have an impact on routine performance.
16. Change
Type 1:
• Changes that are within already proven ranges (within the procedure's design space) are considered
adjustments and do not require a procedure performance qualification study to be performed before
returning to routine monitoring.
Change
Type 2:
• These are changes that are outside the already proven ranges but require only confirmation that the
procedure continues to generate data that meet ATP requirements. Full procedure redevelopment is not
required.
Change
Type 3:
• These are changes that involve the need to operate the analytical procedure in a different environment.
These types of changes traditionally have been treated as a procedure-transfer exercise (or procedure
verification when a pharmacopeial procedure is used for the first time in a new environment).
Change
Type 4:
• This is a change that may require a new analytical procedure, but the ATP remains the same. The
procedure will return to the procedure development stage.
Change
Type 5:
• This change involves tightening a specification limit or a change to the intended purpose of the procedure
to measure additional attributes. These changes result in a new ATP being defined.
Continual Improvement - Example of changes and appropriate actions
17. Three Stages in Proposed Lifecycle Approach
Input of Design
Procedure
development
Identify Potential Analytical
Variables
• Continuous Variables
• Categorical Variables
Experimental Robustness Study
Analytical Procedures PPQ Protocol
Experimental studies to
demonstrate “fitness of purpose”
(including local noise factor).
PPQ Report and local analytical
control strategy including the
formal procedure.
Routine
Monitoring
Action
Trigger
Investigation
and CAPP
Special Cause
Variation
Risk
Assessment
Unacceptable
common cause
variation
Continuous
improvement
Stage-1: Procedure Design
Development and Understanding
Stage-2: Procedure Performance
Qualification
Stage-3:
Procedure Verification
Knowledge gathering and preparation (when a procedure
is used in a new location)
Change Type 1
Change Type 2
Change Type 3
Change Type 4
Change Type 5
18. Current Approach
• Focus is showing that various procedure
performance characteristics meet criteria—
but may not consider how these relate to the
overall uncertainty in the data and whether
they are acceptable or not.
Lifecycle Approach
• The driver is understanding the target
measurement uncertainty, which is the
maximum level of measurement uncertainty
that represents fitness for purpose (i.e.,
ensures decisions from data are made with a
predefined confidence) and to demonstrate
the procedure will meet this uncertainty
requirement.
Current Approach
• Tendency to perform validation in a check
box manner against the general analytical
performance characteristics described in and
ICH Q2.
Lifecycle Approach
• Specific ATP for each measurement
requirement defining the characteristics and
criteria that the procedure should meet.
Advantages of Adopting a Lifecycle Approach for Managing Analytical Procedures
19. Current Approach
• Limited understanding of effects of variation
on performance. Lifecycle Approach
• Structured and methodological approach to
identify and explore variables.
Current Approach
• Validation, verification, and transfer are
seen as separate exercises.
Lifecycle Approach
• All are integrated as part of the analytical
procedure lifecycle, and success is
demonstrated by generating reportable
results that are consistent with the ATP.
Advantages of Adopting a Lifecycle Approach for Managing Analytical Procedures
Current Approach
• Confusion about the differences among
procedure validation, procedure transfer,
and procedure verification.
Lifecycle Approach
• Improved clarity and holistic view with the
ATP as the focal point.