Quality by Design

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  • Created by: LBCW0502
  • Created on: 27-11-19 14:11
What is quality by design?
A systematic approach to development that begins with predefined objectives and emphasises product and process understanding and process control, based on sound science and quality risk management
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What are the ICH guidelines? (1)
ICH – International Conference of Harmonisation – guidelines for drug development, agreed by countries, from development to impurities, API manufacture, drug substance, solvents, how to set specifications, science based. Analytical methods, validity
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What are the ICH guidelines? (2)
Public industry (stakeholders) – submit comments about ICH guidelines, review guidelines
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What are the aims of the ICH - new quality paradigm?
Fosters quality by design, continuous improvement and new technology introduction. Promotes more effective use of regulatory agency and industry resources. Enhanced patient confidence on pharmaceutical quality
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Outline the history of QbD
FDA (risk based approach). ICH (new quality paradigm). FDA (guide for industry) - PAT, pharmaceutical manufacturing, QA. EU development of pharmaceutics, principle of quality being built rather than tested
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Who were the inventors of the ICH?
US, Canada, Japan, EU, WHO, Global Co-operation Group
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What are the key guidelines in the ICH new quality paradigm? (1)
Q8 (R2) - pharmaceutical development. Q9 (quality risk management). Q10 (pharmaceutical quality system). Q11 (development and manufacturing of drug substances, chemical/biological)
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What are the key guidelines in the ICH new quality paradigm? (2)
Q12 (technical, regulatory considerations for pharmaceutical product lifecycle management)
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What are the aspects of quality - relevant guidance (ICH)
High level guidance (non-prescriptive), science/risk-based, applicable over entire product lifecycle, intended to enhance pharmaceutical product quality
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Describe features of a dossier (1)
Common technical document. Made up of 5 modules – administrative (module 1), quality (module 3), non-clinical study reports (module 4), clinical study reports (module 5).
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Describe features of a dossier (2)
Quality module – knowledge needed from modules 4 and 5 (e.g. determine if studies have been carried out for safety). Research/discovery, modules format, launch
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Outline the pathway for producing a biologic
Host cell, vectors, gene of interest, expression vector, expression system, master cell bank, working cell bank, culture/fermentation, purification, drug substance, sterile filtration/aseptic filling, drug product. Uses ICH guidelines for steps
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What is the ICH Q8 guideline?
Describes suggested contents for the 3.2.P.2 (Pharmaceutical Development) section of a regulatory submission in the Common Technical Document (CTD) format
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Describe features of ICH Q8 - pharmaceutical development (1)
General principles (components of drug product, formulation development, manufacturing development). New concepts (minimal vs enhanced, design space, regulatory flexibility, RTRT)
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Describe features of ICH Q8 - pharmaceutical development (2)
Annex (clarification of key concepts, description of principles of QbD, examples of how tools/concepts could be put into practice)
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What is the traditional (minimal) approach?
Empirical development, one variable at a time, fixed manufacturing process, focus on reproducibility, off line analysis, QA by testing, reactive lifecycle management (corrective actions)
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What is the QbD (enhanced) approach? (1)
Systematic approach to development. Manufacturing process (and quantitative formulation) adjustable within the design space. Focus on control strategy and robustness of the process. PAT tools used for feed forward and feed back process control
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What is the QbD (enhanced) approach? (2)
Risk based control strategy and potentially Real Time Release. Preventive lifecycle management and continuous improvement
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What is regulatory flexibility? (1)
Risk-based regulatory decisions (reviews and inspections). Manufacturing process improvements, within the approved design space described in the dossier, without further regulatory review. Reduction of post-approval submissions
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What is regulatory flexibility? (2)
Real-time quality control, leading to a reduction of end-product release testing
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What is the risk based approach? (1)
Controls affect, process which affect product which affects the patient - diagram
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What is the risk based approach? (2)
Quality risk management, knowledge management. Product understanding, process understanding, process control, continuous improvement - diagram
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Summarise the ICH Q8 QbD approach
Target the ATPP. Determine CQAs. Link raw material attributes and process parameters to CQAs and perform risk assessment. Develop design space. Design and implement a control strategy. Manage product lifecycle and continual improvement
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What is QTPP?
Quality Target Product Profile - a summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account the safety and efficacy of the drug product
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What is CQA?
Critical Quality Attribute - a physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality
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Give examples of drug product CQAs
Assat, CU, dissolution (affects bioavailability), tablet mechanical strength (withstand transport)
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ICH Q8 - what is potentially critical?
Raw materials, operator. Inoculum, fermenation, separation, extraction, refolding, purification, diafiltration, filtration, drug - diagram
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Describe features of quality control of products derived from recombinant DNA technology
Factors may compromise quality, safety, efficacy - genetic stability, protein, manufacturing procedure, unintended variability in culture, extensive scale-up. Desired quality no just limited to impurities (e.g. antibody diagram)
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Summarise features of CQAs in ICH
Desired finished product. Product related substances not desired. Impurities (product and process related) not desired. Avoid contaminants
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What is a design space?
Multi-dimensional combination and interaction of input variables, i.e. material attributes and process parameters, that have been demonstrated to provide adequate quality. Knowledge space. Design space (provide quality). Control space
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What is the practical implementation of a design space?
Excipients/API/environment/personnel, variable input, locked, variable output (with design space - get predefined output quality)
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Describe features of a design space (1)
Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process. Design space proposed by the applicant, assessed
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Describe features of a design space (2)
Terminally sterilised injectables / Lyophilised injectables / Small molecule API / Monoclonal antibody API. Surface plot - degradants vs pH vs temperature
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What is the ICH Q8 control strategy? (1)
Planned set of controls. Input material attributes (API, excipient, primary packaging). In-process controls. RTRT. End product testing. Based on product and process understanding and risk management. Design space optional, control strategy not
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What is the ICH Q8 control strategy? (2)
Every process and product has an associated control strategy
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What is the ICH Q8 control strategy? (3)
ICH Q10 - pharmaceutical quality system. Assures Process Performance/Quality. Includes control of parameters and attributes related to Drug Substance, Drug Product. Includes components, facility and equipment operations
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What is the ICH Q8 control strategy? (4)
Includes In-Process Controls, Finished Product Specifications and Methods to Monitor and Control
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What is RTRT? (1)
The ability to evaluate and ensure the acceptable quality of in-process and / or final product based upon process data, which typically include a valid combination of assessed material attributes and process controls
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What is RTRT? (2)
Comprise a combination of process controls  utilise Process Analytical Technology (PAT) tools e.g. NIR and Raman spectroscopy (usually in combination with multivariate analysis), together with the control of relevant material attributes
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What is batch release? (1)
Not dependent upon conventional finished product testing. In-process control data. Predictive modelling / Algorithm prediction. Direct measurements e.g. levels of process impurities such as residual Host Cell DNA (HCD) or Host Cell Proteins (HCP)
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What is batch release? (2)
Indirect measurements e.g. process parameters for sterilisation
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What is PAT? (1)
A system for designing, analysing, and controlling manufacturing through timely measurements (during processing) of critical quality and performance attributes of raw and in-process materials, processes with goal of ensuring final product quality
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What is PAT? (2)
An enabling tool to a more systematic approach to pharmaceutical development (QbD). E.g. modify process line with sensory systems. NIR images to analyse API/excipients in tablets
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What are the challenges with ICH Q8 RTRT? (1)
Translation of finished product specification acceptance criteria into acceptance criteria for a RTRT System. Analytic methods (revalidation needed). Adaptation of proven analytical methods. Improve analytical methods. Data overload
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What are the challenges with ICH Q8 RTRT? (2)
Parametric release
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What are the key features of QbD terminology?
QdD, control strategy, design space, RTRT, CQAs (learn definitions of terminology)
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What are the links between RTRT, control strategy and QbD?
RTRT is part of control strategy (CQAs). QbD not directly correlated to RTRT. Design space not required for RTRT
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How is QbD implemented? (1)
Drivers (proactive, address regulatory trends, number of reworked batches, better manufacturing/robust process, low recalls, leaders in field). Expectations (faster approval, fewer variations, improved tech, high compliance, fewer inspections)
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How is QbD implemented? (2)
Greater regulatory flexibility, higher return on investment. Selecting drug candidates (source, marketing, type of drug, generic, sterile/non-sterile, formulation). QbD organisation/mindset (expertise, resources)
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Other cards in this set

Card 2

Front

What are the ICH guidelines? (1)

Back

ICH – International Conference of Harmonisation – guidelines for drug development, agreed by countries, from development to impurities, API manufacture, drug substance, solvents, how to set specifications, science based. Analytical methods, validity

Card 3

Front

What are the ICH guidelines? (2)

Back

Preview of the front of card 3

Card 4

Front

What are the aims of the ICH - new quality paradigm?

Back

Preview of the front of card 4

Card 5

Front

Outline the history of QbD

Back

Preview of the front of card 5
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