Pharmaceutical Quality by design (M4)

Question 1

What does this tell us?

Answer 1

• Biotech and pharma have a much tighter spec/standards to adhere to (2 sigma rather than 4) which results in a lot higher spending, ppm defects and lower yield

Question 2

The ICH (international conference on harmonisation) is a forum between EU, USA and Japan to discus what?

Answer 2

• To increase international harmonisation of technical requirements
• To ensure safe, effective and high quality drugs are developed

Question 3

What does this new framework tell us?

Answer 3

• Integrate process understanding over all the regulation, quality systems and improvements, instead of compartmentalising it
• Instigating change rather than seeking approval for change will speed up the rate of drug development
• All this minimises risk

Question 4

What is the definition of quality by design

Answer 4

A sysematic approach to development that begins with:
- Predefined objectives
- Emphasised product and process understanding
- Process control
Based on quality risk management

Question 5

What is this?

Answer 5

This is the proposed design space
- 2 Parameters are set along the axis and an acceptable region for each variable being tested is found (eg. friability and dissolution)
- These regions are plotted on the graph with the overlapping section being the net acceptable region when considering both variables

Question 6

What are the 2 principles of quality risk management?

Answer 6

1) The risk to quality should be based on scientific knowledge and always link to patient protection (PRAS, DRAS)
2) The level of effort and documentation of risk management should be appropriate for the level of risk

Question 7

What does this tell us about ICH 9?

Answer 7

• Focussed on linking quality and the level of risk must be linked back to the patient across the whole process
• Eg. dRAS (design risk assessment, always linked how the design could harm the patient, same for pRAS)

Question 8

What is the general structure for a risk management procedure?

Answer 8

1) Risk assessment (identify and evaluate the level of risk)
2) Risk control (reduce the level of risk to an acceptable level)
3) Document the change and review the events

Question 9

What is GMP?

Answer 9

Good manufacturing practice

Question 10

What are ICH Q8-11?

Answer 10

These are guidelines that cover pharmaceutical development, quality risk management, and regulatory considerations for pharmaceutical development.

Question 11

What is meant by quality by design?

Answer 11

a systematic and scientific approach to drug development and manufacturing that emphasizes building quality into the product from the outset rather than attempting to test quality into the product after it has been manufactured.

Question 12

Explain each phase in the QbD framework

Answer 12

1) QTPP (Quality Target Product Profile), this is what is needed of the drug, dosage, delivery system, stability
2)CQAs (Critical Quality Attributes) - These are attributes that must stay within narrow parameters as they are critical to the quality of the product
3) CPP - (Critical Process Parameters), These are process parameters whose variability has an impact on the CQA and so need to be monitored
4) Monitoring if the design space, which means applying analytical technology methods to analyse the interaction and combination effects on the input variables and process parameters
5) Control strategy, Outline a set of controls that ensure the process performance and quality product stay within the design space
6) Continuous improvement

Question 13

What is meant by QTPP?

Answer 13

Quality target product profile
summary of the quality attributes that a drug product should ideally possess to meet the intended therapeutic objectives

Question 14

Give some examples of QTPP (quality target product profile) attributes that a drug should posess?

Answer 14

• An appropriate dosage strength
• An appropriate route of administration and delivery system
• Physical attributes such as appropriate dissolution and disintegration rates

(Anything that the drug should do)

Question 15

Complete the following QTPP table for a typical tablet

Answer 15

Any attributes that the drug should ideally possess would be acceptable

Question 16

What guidelines has ICH Q8 set?

Answer 16

• The QbD framework

Question 17

What guideline has ICH Q9 set? and what are these?

Answer 17

• A QRM (Quality Risk Management) strategy
  1) Identify the risk level of a process
  2) Employ a strategy to reduce this risk level to acceptable
  3) Review the results of this strategy

*If any steps fail go back a step

Question 18

What guidelines has ICH Q10 set?

Answer 18

• A PQS (Pharmaceutical Quality System)
  A quality change management system, eg, windchill, the system needs any changes to process, design or product to be reviewed and approved by quality engineers to monitor its effect on QTPP, CQA and CPP

Question 19

What guidelines has ICH Q11 set?

Answer 19

Q11 offers guidelines for pharma companies to help make and control the active ingredient (API) in their products

Question 20

Why might a design of experiment methodology used?

Answer 20

• CPPs are often interlinked and changing one can affect another
• The DoE approach looks for interaction effects between different CPPs to help establish a clear design space

Question 21

What are some example CPPs for wet granulation?

Answer 21

• Mixing speed
• Rate of adding wetting agent
• Mixing time

Question 22

What was the purpose of doing the International Conference for harmonisation?

Answer 22

To align international drug manufacturing standards and regulations

Question 23

What is QTPP? with an example

Answer 23

Quality Target Product Profile:
The intended drug characteristics and therapeutic effects
- Eg a certain tablet hardness, dissolution rate of 4, shelf life of atleast 4 weeks

Question 24

What is CQA? And how does this link to the QTPP?

Answer 24

Critical Quality Attributes
The chemical, physical or biological properties that are critical to the quality of the drug, also a failure in achieving one of these attributes could have an impact on patient health
Some of the important QTPP will feed into the CQA

Question 25

Give an example of a CQA?

Answer 25

• Dissolution rate below x
• Bioavailability of x
• Tablet density of x

Question 26

What is a CPP? And how does this link to CQA?

Answer 26

Critical Process Parameter
These are process parameters that need to be defined and controlled to a set tolerance or it may compromise the CQA, - This has a knock on impact on patient health

Question 27

Give an example of a CPP?

Answer 27

• A specific compression force may be required to achieve a CQA of x density

Question 28

What is meant by design space?

Answer 28

• This is the flexible space in which the manufacturing process parameters and material attributes can be changed while still being in the acceptable region ensuring product quality
• Process tolerances the interaction effects must be clearly defined to establish a design space

Question 29

What is meant by control strategy?

Answer 29

This is a strategy based on process knowledge, employed to ensure that the CPP stay within tolerances, quality and performance to ensure the process as a whole is kept within the design space

Question 30

What is meant by continual improvement?

Answer 30

This means conducting on going risk evaluation to all aspects, the process, the product and the strategy to improve

Question 31

What are the fundamentals of QbD?

Answer 31

• Start by looking at what the patient needs
• Defining clearly CQAs, CPPs and a control strategy
• Continual Risk assessment to establish a design space
• Control strategy is essential
• Exchange of info between R&D and manufacturing is crucial