Seminar Tanja and Lauterbach lecturs Flashcards
Defination of QC
it is system of maintaining standards in manufactured products by testing a sample of the output against the specification
What is analystical Quality Control
we have the QC in life science and instrumental analysis
QC in life science is for
Screening for impurities, determining API concentration
checking of compliance against standards
instrumental analysis
Chromatography
Spectroscopy
Crystallography
on what is AAS based on?
it is based on the fact that atoms in the ground state can sbsorbt certain wavelengths of the elctromagentic spectrum between 190 and 850 nm
What is observed in AAS and why
in AAS lower atomization temperatures are applied in comparison to AES
Most of the atoms are in the ground state and only transitions that emanate from the ground state , so-called resonance transition are observed
Areas of application in AAS
enviromental monitoring, food ontrol, material sciences, clinical chemistry, QC
What is validation?
provides a high degree of assurance that a specific process/method will consistently produce a product metting its predtermined specifications and quality attributes
Types of Validation
Process, cleaning,computerized system validation
Process Validation
is a data collection and assessment from production through to commerical manufacturing
Cleaning validation
methods must verift that coontamination and cross contamination from previous productions would be prevented
Computerized system validation
evaluation regarding their application, production and QC
what’s the purpose of Computerized system validation
it is to verify that the computerized system specification are appropriate for the user’s needs and intended use.
Method Validation
process of demonstrating that an analytical procedure is suitable for its intended purpose
three key words in process validation
documented evidence of the process, perform effectively reproducibly and so meeting the predtermined specifications
What is the importance of analytical procedure?
it is test a defined characteristic of the drug substance or DP against established acceptance criteria for that characteristic
what are validation characteristics
accuracy precision linerity specifity range robustness LOD LOQ
accuracy defination
closeness of agreement between the value which is accepted (concentration true value or accepted reference) and the value found
Precision defination
closeness of agreement between a series of measurements obtained from multiple sampling of the same homogeneous sample
repeatabilty
same operating conditions
reproducibility
between laboratories
Guidelines for Qualifications
EudraleX Volume 4, Annex 15, ICH, FDA, Active agent manufacturing regulation
Purpose of Q and V
Q: documented evidents that equipment is delivering expected results
V: documented evidence that the methods or processes deliver expected results by using defined equipment and parameters
Intended use of Q and V
Q: Facility, equipment, system
V: processes, method
Responsibility for Q and V
Q: Head or production and head of QC
V: Head of QC (theoretical), futher department (practical)
What is necessary before qualificationa and validation?
assessed for its risk by means of risk analysis tools, FMEA
what is verification
Verification is when a pH.Eur. method is used
(compendium method), the applicants have to show that the method used is verify
What does a qulification of an impurities mean?
You have to garantee that your impuries don’t excess the threshold
what’s the goal of validation
Is not to showed that your method, rather it must work inroutine practise, change of person, sites and parameter. it is un-going process, work under route and not ideal conditions
when sould methods be validated
Established methods, Revision of established methdos, method changes, comparison of methods, new method development
new reulatory guidelines
ICH guidlines for validation means one has fulfilled everything
it is not a checklist, deviation from the guidline is allowed but has to be justified
What is a Re-validation?
Applicant ahs to make sure that the actuality producer is working
Who us responsible for the kind of the validation procedure used?
the responsibility is of the applicant
Types of analytcial procedures to be validated
identfication of your product
qauntitative test
quantitative tests for impurities
what kind of test for impurities is possible?
Either a quantifiction or a limit test
what parameter is not part of the validation characteritics?
System suitability testing
What is Specificity?
the method is specific if in the present of other compounds, one is able to still detect the compound to be analysed
test for Specificity?
identification
purity tests (content of impurities)
Assay (content or potency)
Determination of your assay
Separation factor and reolution
Separation factor
ratio of the retention factors of two peaks but doesn’t consider overlapping of peaks
Resolution
it is better,because it consider width of the peaks
Determination of resolution
used of the width weight, the width of the maximum of the peak
learn to caculate the separation factor and resolution
SP= t(2)- t(r)/t(1)-t(r) R = t(2)-t(1)/ 0.85 (w (1/2)2 + w (1/2)1)
peak purity
designed to detect the present of an impurity
why is specificity-peak purity the important
because the peak quality is not always a garantee of the purity of the peak
one has carry out Mass spectrometry
what does the specificty assay of purity tells us?
impurities are available or not available
Impurities are available
demonstration of the discrimination of the anlyte in the presence of imurities and or excipients by spiking pure drug substance or DP with appropraite levels of impurities
Impurities are not available
comparison of the test results o samples possibly containing impurities to a second well-characterized procedure
Recommended data to assess accuracy
assessment of a minimum of 9 deteminations over a minimum of 3 concentration levels
to be reported as percent recovery by the assay of knwon added amount
Recommended data to assess precision
SD, RSD
What are the three levels of precision
Repeatability
Intermediate precision and reproducibility
different between Intermediate precision and reproducibility
laboratory and apparatus are same, while for reproducibility everything is different
what are the critical variation for roobustness for LC
variation of ph in a MP, MP composition, different columns, temperature and flow rate
what are the critical variation for roobustness for GC
Different columns, temperature and flow rate
impurity quantitative and assay
accuarcy and precision
Specificity is determined by?
identification, impurity quantitative and qualitative and assay
LOD is used for?
impurity qualitative
for what is the LOQ used for?
No identification, but for impurity determination and assay
For what should the minimum specified ranges be consider
Assay ( DS and DP)
content uniformity
impurity quantitative: LOD and LOQ
Definition of Specifications
list of test, references to analytical procedures and appropriate acceptance criteria to which a DS or DP should conform for its intended use
proposed specifications
it is proposed and justified by manufacturer, to be approved by regulatory authorities
Specification and CT
it does not address the clinical research stage
Which test and acceptance criteria are appliable for new NDS and P
Description, identification , assay and imprities
Which test and acceptance criteria are appliable for new chircal NDS and P
identity, assay and
Legislation for specification for impurities/ degradation products
ICH Q6A
ICH Q3A(R2)
decision tree or impurities in New drug substance
ICH Q3B(R2)
Impurities in New Drug product
What are the threshold for impurities
Reporting, identification and qualification threshold
Reporting TH
A limit above which an impurity should be reported but not identified
Q TH
TH, above which the impurity should be qualified
What is important when using pH.Eur method?
thoes method are already validated, but there need to be verify
Reference standard
primary (100 % purity, identity must be confirmed
secondary, working standard
what are the three options of MAH to demonstarte the quality of their substances (Ph.Eur.)
Certification of suitability or CEP procedure
the active substance master file (ASMF) procedure
Compilation of the full dossierr for the chemical susbtance
CEP procedure
MAH submit application to the EDQM describing the manufacturing process for the substance
CEP and MAA
MAA can use the CEP as reference
Purpose of the Cerificate of suitability
protection of intellectual property and know how of manufacturer
what’s the responsibility of a CEP holder?
it has to prove the EDQM with a qulity dossier demonstrating the suitability
Who has access to the CEP information
just the CEP holder and not the MAA and MAH
Objective of the Active Substance Mater file (ASMF)
protection of intellectual property
Restricted part of the ASMF
Manufacturng process, process validation
justification of specification
QA?
their task is to ensure that a product under development meets specified requirements
Prevention of failure
QC?
they ensure that a manufactured product adheres to a defined set of quality criteria
Detection of failure
Focus of QA and QC?
QA: prevent defects
QC: identify detects
what is the Goal of QA and QC
QA: to improve development and test processess
QC: identy defects after a product is developed and fore it’s released
How does the QA, and QC works?
QA: establish a good management system, continuous monitoring
QC: Finding sources of quality problems
What are the key points of QA and QC?
QA: prevention of quality problems
QC: maintain the product quality using analytial techniques
responsibility QA and QC
QA: everyone
QC a specific team
As a tool QA, QC
QA managerial rool
QC corrective tool
