Process Development

Question 1

What Dictates Quality by Design

Answer 1

ICHQ8 (Pharmaceutical Dev), ICHQ9 (Quality Risk Management) and ICH10 (Pharmaceutical Quality System)

Question 2

Quality By Design Principle

Answer 2

Quality built into product through understanding it and it’s manufacturing & development process. Understanding risks involved in manufacturing leads to mitigation

Question 3

Quality By Design Cycle Steps

Answer 3

QTTP, CQA, CMA + CPP link to CQA, Establish Design Space, Establish control startegy and Product Lifecycle management. Iterative (continuos) process

Question 4

Quality Target Product Profile (QTPP) Outline

Answer 4

Summary of drug product quality characteristics. Ensures desired quality, safety and efficacy when met

Question 5

Critical Quality Attribute (CQA) Def

Answer 5

Appropriate range & distribution of physical, chemical, biological and microbiological properties of product quality

Question 6

Critical Material Attribute (CMA) Def

Answer 6

Material attributes whose variation directly impacts critical quality attribute. Needs to be controlled to ensure product quality

Question 7

Critical Process Parameters (CPP) Outline

Answer 7

Process parameters whose variability has direct imapct on critical quality attribute. Needs to be controlled

Question 8

Design Space Outline

Answer 8

Multidimensional combination and interaction of material attributes and process parameters and have been demonstrated to provide quality assurance

Question 9

Traditional (quality/baseline) Characteristics

Answer 9

Empirical (univariant) pharmaceutical dev, Fixed manufacturing process, In process testing, Product specification (1st line control), Intermediate & end product testing, React to problems

Question 10

Quality Based Design (enhanced) Characteristics

Answer 10

Systemic (multivariant) pharmaceutical dev, Adjustable manufacturing process, Process analytical tech process control, Product specification of 1 strategy, Risk-based control strategy and Continual improvement

Question 11

Process Analytical Technology (PAT) Outline

Answer 11

What is measured throughout manufacture. Eg; IR probe for real time measurements

Question 12

Impact of Using Enhanced Approach

Answer 12

Regardless of input variability, the output will be of pre-defined (predictable) quality. Due to process variability (with realtime monitoring) in design space

Question 13

Process Development Def

Answer 13

Pharmaceutics stage that starts after product formulation design & optimisation. Ends when manufacturing process has been designed and optimised

Question 14

Novel Product Dev Stages

Answer 14

Product Formulation, Process Dev, Process Scale-Up, Production Scale Manufacturing and Process Control

Question 15

Process Development Department

Answer 15

Formulation Dev, Procurement, Production, Engineering, Health & safety, Planning, Validation, Quality Control Labs and Quality

Question 16

Research Outline

Answer 16

2 stages: product and process. Understanding; QTTP, CQA, CPP, CMA, raw material specifications, handeling safety, equipment requirements and qualification work exteny

Question 17

Process Research

Answer 17

process investigation, examine equipment capabilities, equipment qualification status, examine existing utilities and benchmark similar technologies

Question 18

Product Reserach

Answer 18

formulation, pharmaceutical & pharmacological, raw materials and finished product.

Question 19

Tablet Process Endpoints

Answer 19

Apperance, Identification, Water Content, Content Uniformity, Antioxidant Content, API Assay, Degradation Products, Dissolution and Microbials Levels

Question 20

Process Design Flow

Answer 20

Select Process Parameters, Risk Assessment, Trials (lab/piolet/full scale), process capability analysis, process reproducibility (if no: return to beginning) and Process Dev Reports

Question 21

Process Parameters

Answer 21

Steps of process. Need to identify what will impact critical product attributed. Eg; mixing speeds

Question 22

Failure Mode & Effect Analysis (FMEA)

Answer 22

Formalised technique that enables assessment for manufacturing process. Creates corrective actions to; eliminate failure causes, reduce failure probability and increase detection

Question 23

Risk Priority Number (RPN) Outline

Answer 23

Probability (1-5) X Severity (1-5) X Detectability (1-5). Min risk = 1, Max risk: 125. Part of FMEA

Question 24

Trial Execution

Answer 24

Establishes: normal operation limits for process parameters and proven acceptable ranges. Consider multivariate analysis. Steps; setting, normal limit operation and proven acceptable range

Question 25

Process Capability Analysis

Answer 25

Statistical measure of degree to which process meets requirements

Question 26

Process Development Reports

Answer 26

gathering info for trail batched, circling back to risk assessment and addressing undesirable results

Question 27

Process Performance Qualification

Answer 27

Action proving and documenting a process. Product meeting is predetermined specification and quality attributes

Question 28

Process Performance Qualification Protocol Steps

Answer 28

Manufacture & test piolet batch (witn statistical analysis), prepare process performance qualification report and Update: Dev report, CPP & CMA Document, master batch record and control strategy

Question 29

Process Control

Answer 29

Control strategy implementation, Continuos process verification abd Product life cycle management