PAT & QbD Flashcards
What is PAT?
Process Analytical Technology - A means of analysing and monotoring a process using offline, at-line and online measurements/ techniques
Why does the FDA recommend a QbD approach?
The focus is that quality should be built into the product with a thorough understanding of the product and process by which it is developed and manufactured along with a knowledge of the risks involved and how best to mitigate these
Commonly used PAT instruments
- Near Infrared (NIR)
- Mid IR
- UV/Visible
- Raman
- Lasentec (FBRM)
- Mass Spec
What needs to be considered when interfacing measurement techniques into the process?
- Location of spectrometer
- Representative Sampling
- Safety & Atex rating
- Type of interface (e.g. dip pipe, by-pass loop, probe, flow cell)
What is SAM-Spec?
Spatially Advanced Measurement by Spectroscopy - measurements taken at several distances for physical or chemical characterisation, homogeneity and uniformity.
- Can check for cracks in tablets, API content or particle dispersion
What and how is monitored in reaction processes?
Initiation, Impurity levels and End point
- UV
- NIR
- Mid-IR
- Mass Spec
What and how is monitored in crystallisation processes?
Particle size & End-point
- FBRM
- UV
- NIR/ Mid IR
What and how is monitored in distillation processes?
Composition Control and End point
- NIR
- Mid IR
What and how is monitored in Form Control processes?
Completion
-NIR/ Mid IR
What and how is monitored in drying processes?
Crystal attrition & End point
- NIR
- Mass Spec
What and how is monitored in blending processes?
Water Content & End Point
-NIR
What and how is monitored in tableting processes?
API Content, Content Uniformity, Weight/density/integrity
- NIR
What is PCA?
Principal Component Analysis (PCA) is the analysis of a single data set. It is a means of reducing dimensionality to a number of variables where a clear distinguishable behaviour trend can be seen. (Unused axes or data points close together contain similar information and the closer they are to the origin the les the influence the model)
What is PLS?
A Partial Least Squares Model is built by taking spectra of known, well characterised materials and then comparing data acquired during the process to this model to predict component concentrations (it is a methof of multivariate regression)
Define QbD
A systematic approach to development that begins with predefined objectives and emphasises product and process understanding and a process control strategy based on sound science and quality risk management
Define Control Strategy
A planned set of controls, derived from product and process understanding that assures process performance and quality
Define Critical Quality Attribute
A physical, biological or microbiological property that should be within an appropriate range/distribution to ensure product quality
Define Critical Process Parameter
Process parameter whose variability has an impact on a CQA and so should be monitored or controlled to ensure the process delivers the desired quality
Edge of Failure
The boundary to a variable or parameter beyond which the relevant quality attributes cannot be met
Proven Acceptable Range (PAR)
Range of a process parameter within which will result in the product meeting the relevant quality criteria
Elements required in QbD
- Defnine the QTTP
- Identify the CQAs
- Selecting the appropriate manufacturing process
- Identifying a control strategy
- Identifying the CPPs and CMAs
- Determing the functional relationships between teh CMAs/CPPs and CQAs
- Establish an appropriate control strategy using process understanding
What are the steps in QbD?
- Identify QTTP & CQAs
- Selection of hte synthesis routes
- Gaining the experimental knowledge to determine the proven acceptable ranges (PARs)
- Develop the control strategy
- Technology transfer from the development to the manufacturing business
- Manufacture of marketable product and regulatory submission
What is the use of performing a risk assessment?
Helps identify and rank which material attributes and process parameters have an effect on the CQAs
Define Design Space
Multidimension and interaction of CMAs and CPPs that have been demonstrated to provide assurance of quality
Two approaches to delveloping a quantative model
- First Principles: derived from an understanding of underlying science
- Empirical Modelling Approach: DoE studies obtaining data which is used to derive both the form of the model and its associated coefficients
Describe Parrallel Coordinates
A set of parallel axes on which data points are represented by a line that connects the corresponding values for each variable
(Used to represent the design space and ensure continuous verification within its limits)
What are the 3 modes of control
Attribute Control
Parametric Control
Procedural Control
Define Attribute Control
Testing of materials reagents and drug substances to specifications using online/offline techniques
Define Parametric control
Application of the proven acceptable range limits to process parameters in the design space
Define Procedural Control
Control based on process knowledge e.g. order of addition of material, work up procedures etc
3 Steps of Process Validation
- Process Design - PRocess is defined based on knowledge gained throuch scale up activities (QbD)
- Process Qualification - Design is confirmed as being capable of reproducible manufacturing results (Tech Transfer - Point of Commercialisation)
- Continued Process Verification - Ongoing assurance that the process is controlled (Commerical Manufacture)
2 Phases of Process Verification
- Achieiving the point of Commercialisation (acquired enough data and knowledge about the process for approval)
- Continual verification or monitoring of quality indicator data changes during the production process to demonstrate the process continues to work as intended
Define unit operations
The process steps involved in the API synthesis and tablet formulation. E.g chemical reaction, crystallisation, distillation, drying, blending, tabletting
