MDM: PO, SU, VAL

Question 1

1. What is process optimisation?
2. What does it mean?
3. What dose it lead to?

Answer 1

1. Maximising number of batches which pass release specifications OR maximising number of doses per unit time passing release specifications
2. Reduced quantity of materials used OR reduced production time
3. Reduced waste OR making sure we get the same thing each time

Question 2

1. What is validation?
2. Why do we need it?
3. What does it lead too?

Answer 2

1. Formally doccumented, predetermined success criteria, part of the QA
2. Reproducibilty and to be able to confidently state the system gives the expected results
3. Quality product, wihtout full end of process testing

Question 3

1. What is scale up?
2. When does it occur?
3. What need to happen at each stage?

Answer 3

1. Transferring a process from one batch size to another because the compnay needs to increase number of production units
2. Research (<1g), Development (1g -1000g), Clinical P1 (1kg - 2kg) P2/3 (10kg - 100kg), full scale (>100kg)
3. Process optimisation needs to occur at each stage process and validation of the optimised process needs to occur

Question 4

How do we process optimisation?

Answer 4

• Once manufactuing method has been designed we identifiy critical processes - ones which if not controlled could have a detrimental effect on the product
• Time and temperature usually critical (max/ min temp?)

Repeat evlaution stage for each variable in the process

Question 5

When scaling up what needs to occur for CT productions?

Answer 5

• Increase batch size
• USe different equipement
• monitor manufactuing process carefully
• Make sure critical factor checked
• dissoluton drug sample after 10 minutes at 75C and carrry out assay
• monitor cooling stage

Question 6

When scaling up what needs to be done for larger scale or process transfers?

Answer 6

• Different equipment used
• increase batch size
• 1/10th of full scale
• incoperate more rigorous testing regimes
• validation bataches or piolet batches
• must be done triplicate

Question 7

What is optimisation of process flow and why is it important?

Answer 7

• Movement of batches costs money and problems (segregation)
• Facilities must be desgined in so to minimise movement of products

Question 8

What must process flows be?

Answer 8

• logical
• take into consideration people, processes, materials, products, waste
• Must have a production flow diagram

Question 9

What can be validated?

Answer 9

• Equipment
• cleaning
• processes
• systmes
• facilities

Question 10

Who can validate?

Answer 10

• Quality Assurance department
• Engineering staff
• production staff
• Validaition specialists
• doccumentation specialists

Question 11

How is validation done?

Answer 11

• Instalation qualification
• calibration qualification
• desgin qualification
• performance qualification
• operational qualification

Question 12

What is design quality?

Answer 12

• ensures quality built into the design
• suitable for use in GMP enviroment
• In accorance with desgin specifications and intentions

Question 13

What is installation qualification?

Answer 13

• Ensures the right thing has arrived
• ensures it meets specificatinos of DQ and GMP requirements
• Has been installed as directed
• Calibrations have been done, with certified, tracable standards used

Question 14

What is operational qualification?

Answer 14

• Checks equipment works under power
• performed without material or placebo
• Assess stability of equipment

Question 15

WHat is performance qualification?

Answer 15

• Testing actual production process
• each stage of process evaluated
• determine of critical factors
• assess effects of variability of critical factors

Question 16

What people are invoved in the scaling up process

Answer 16

• Research - pharmacologists, synthetic scientists
• development - analytical and development chemists
• production - manufacturing personel, technology transfer scientist

Question 17

What doccumentation is there for scaling up process?

Answer 17

• Master batch doccuments
• specifications
• validation doccuments

Question 18

What is a good process

Answer 18

• Reproducible
• product stable over full shelf life
• reproducable
• as simple as possible

Question 19

What liquid dosage forms is there?

Answer 19

• emulsion
• suspension
• simple liquid
• parental

Question 20

What solid dosage forms is there?

Answer 20

• tablet
• capsule
• pessaries

Question 21

Describe steps to make a supository

Answer 21

Question 22

Describe steps to make a granulation

Answer 22

Question 23

1. What is change control?
2. Why?
3. How?

Answer 23

1. A system to evalusate consequences of change before they are implemented
2. to prevent mistakes or costly revalidation exercises
3. Proposed changes doccumented and evalusated before implemention

Question 24

1. Why revalidaiton?
2. How often?
3. What?

Answer 24

1. To ensure system is maintained in a validated state
2. depends on many factors
3. Depends on what has happened to the equipment, system, process since last validated

Question 25

What is calibration?

what are the instrament categories?

Answer 25

1. The set of opperations which establish the relationship between values indicated by a measuring instrament/system to the corresponding values of a known reference standard

• Critical - effect on both process and product (6 monthly)
• Major - effect on either Process or product (annualy)
• Reference - no effect on process or product (on instalment)

Question 26

1. What is a VMP and what should it contain?

Answer 26

• A Validation Master Plan (VMP), a part of GMPs , is a document that outlines and defines the processes and equipment that are to be validated and the priority and order in which this will be don

The VMP or equivalent document should define the qualification/ validation system and include or reference information on at least the following:

• Qualification and Validation policy;
• The organisational structure including roles and responsibilities for qualification and validation activities;
• Summary of the facilities, equipment, systems, processes on site and the qualification and validation status;
• Change control and deviation management for qualification and validation; Guidance on developing acceptance criteria;
• References to existing documents; The qualification and validation strategy, including requalification, where applicable.

Question 27

1. What are the three types of process validation which can be carried out and how do they differ?

Answer 27

• Traditional – a number of batches of finished products are manufactured under routine to conditions to confirm reproducibility
• Continuous – used where product has been developed by a quality by design approach
• Hybrid – hybrid of continuous and traditional approach. Used where there is substantial product and process knowledge

Question 28

1. Why does cleaning validation need to be carried out?

Answer 28

Cleaning validation should be performed in order to confirm the effectiveness of any cleaning procedure for all product contact equipment.