Process Validation Flashcards
What are arease of the validation master plan?
Media systems, production plants, Hygiene Master plan, process validation and computerized system validation
What the traditional process validation way?
the process was carried out and the quality of the final product was tested with 3 commercial batches. if the validation was sucessful, no further validation was needed
How was the process define in the traditional process validation?
the process was define by the quality of the product
What is the different to today’s process validation in comparision to the TPV?
we have the specify proces controls by assessing the process capability
why the TRV not optimal?
because there is not enough interactions between process parameters and quality attributes of products
What is used to address the process validation?
the life cycle approach
in which guidelines is the LCA meantioned?
FDA and EMA: process validation
What are the three phases of the PV
- Process Design
- Process validation
- Continued Process verification
How can you summarized the LCA?
Validation is a three phase continous process with ongion effort for the entire life cycle of the product
What happend in phase 1
Process Design: the research and development phase, which involves defining a process for manufacturing of a product
what are the process that are define?
QTPP, CQAs, CPPs, Conducting risk assessments and control strategy id defined
Was has to be consider in the regulatory point of view?
an essential component of this stage is meticulous and comprehensive record keeping
What is a QTPP and where is it define?
it is a prospective summary of the quality characteristics of a drug product. it is carry out to ensure the quality of the product and so taking into account safety and efficacy. is the defin in ICH Q8 (R2) guidline
What is the CQA?
a physical, chemicl or biological or microbiological property or characteristic that should b within an appropriate limit range, or distribution to ensure the desired product quality
which steps has to be establish to understand a process?
identify of CMQ and CPP Use of risk assesssment levels or range of these risk attributes Design and conduct experiments (DoE) Analyze the experimental data (CMA and CPP) Develop a control strategy
why do we perform a RA?
to identify the high risk steps that may affect the CQA of the final drug product
which steps are part of the control strategy?
Raw material,
quality attributes (in-line, on-line or at-line)
Process parameters
intermediates
enviromental factors
Alorithms to adapt procesess based on applied PAT
CAPA
Summary of phase 1: process design
- Manufacturing process is defined
- CQA’s are identified
- Process knowledge is estabilshed
- Control strategies are specified
Phase 2: porcess validation includes?
building and facilities
transportation of raw materials
knowledge, traning
What does the validation strategies prove?
that a porcess is robust, resulting in consistent product quality
What are the steps in the EMA guideline on process, regarding the traditional process?
Traditional developmenzt
Traditional validation
Validation batches
What are the steps in the EMA guideline on process, regarding the today’s approache?
Quality by design development
continous process verification
verfied control strategy
what is the QbD?
process comprehesion, obtaining knowledge such as
the sequenceof the production steps during manufacturing
most important and critical process parameters(CPPs)
interrelation betweent theCPPs and their impact
what happend after creating the DS?
different CPPs and other infuencing factors are combine
product quality is still verified
what happend after defining and approval of your DS?
changes within the DS are not desined as changes of the production process and no frther authorisation is required
What do you used to do create the DS?
DoE
what’s the advantage of the DoE?
one gain great possible knowledge about the interraltion between infuencing variables and outcomes
to differentiate between significant and insignificant factors
Summary of the Phase 2 is?
-continous verification or traditional approcach
qualification of premises
implementation of the control strategie
what are the main step in the CPV?
it involves ongoing validation during production and to obatined consistent quality
what is the aim of CPV?
detect and resolve process drift
what does the CPV involves?
product sampling, analysis and verification
what is required at the CPV?
an comprehensive record-keeping
What are the elemnts of CPV
ongoing comparsion of CQA and CPP
quality control charts
evaluation of process capability and analysis of trends
ongoing comparsion of CQA and CPP means?
in-line/on-line monitoring of the process
carefully designed smapling procedure (off-line/at-line)
evaluation of process capability and analysis of trends
Data distribution based on random errors or systematic errors
stable and controlled procesess?
Why do we used quality control charts?
it helps to visaulize the behaviour of processess
which variation can occured and which is okay in a process?
Random and specific variation, where the random variation is okay
1 point more than 3s from the centerline indicates?
indication of a displacement of the mean, standard devaition or single outlier in measurement
9 suceesive points on one side of the centerline indicates?
sfift of the mean value
6 consecutive points all increasing or decreasing siginfy?
a trend
14 consecutive points, alternating up and down signs?
that the date comes from two different sources
the QCC is devided into?
shewhart/ process behaviou-QCC and Acceptance CC
shewhart/ process behaviou-QCC is devided into?
Qualitative and quantitative attribues
Acceptance CC is an
Quantitative attribues CC
example of a Qualitative attributes chart
x-QCC, p-chart, c-chart
Quantitative attributes chart is devied into?
Simple, Double and QCC with memory
Simple QCC example
x, x-bar, s and R chart
Double QCC example
x-bar and s-chart
x-bar and R-QCC
QCC with memory
Cusum, EWMA and Mosum
What are process capability
have to still write
summayr of phase 3
- assessment of process-related information
- statistical trend-and failure analysis
- change control
- re-validation after critical changes
what are the changes made during the PV?
frim a selective, temporarliy limited project towards a central tool for qA, continuously supporting a process or product during its lifetime
other changes are?
Life-cycle approach instead of isolated actions
continuous evaluation of data instead of collecting evidence
Risk-based actions instead of maximal completion
