Sterile Manufacturing 3

Question 1

What are the types of cleanroom areas?

Answer 1

Conventional / Turbulently ventilated cleanrooms / Non-Unidirectional air flow
- air is turned over

Unidirectional / laminar / ultra
- achieve a direction of flow, pushing in one direction

Question 2

Conventional cleanrooms

Answer 2

Similar to general ventilation system except

1. Increase air supply
2. HEPA filters (removes 99.97% or particles > 0.3micrograms)
3. Pressurised to keep dirty air out
4. Constructed of materials which don’t generate particles and are easy to clean

• air entry from top
• single point of entry
• operator and equipement points
• turbulent zones = areas of recirculating air (this may contaminate the product and may not be up to standard)

Question 3

What are conventional rooms dependent on?

Answer 3

Total vol of air supplied and the number of particles generated by equipment and operators

Question 4

Unidirectional cleanrooms

Answer 4

Flow of air in one direction (horizonfal or vertical)
Uniform speed (mustn’t be too fast as it will be too turbulent and blow the air away and if too slow we won’t achieve what we want)

Benefits = much better environment to work in as no turbulent zone

Question 5

Vertical unidirectional cleanrooms

Answer 5

HEPA filters in ceiling releasing air down

Deflection of material over operator and equipment = generate area to work safely of a high enough standard

Question 6

Mixed flow room

Answer 6

HEPA filters directly over area where we manipulate product

Question 7

Why are isolators used?

Answer 7

Keep the operator safe when manipulating the product

(Protect product and operator from each other)

E.g. for cytotoxic agents

Question 8

How do isolators work?

Answer 8

Operator works through glove into a sealed high quality area
No need to wear goggles or masks because the product is sealed away so that minimises the clothing required

Question 9

When should an operator wear full protective clothing?

Answer 9

When producing antibiotics = minimise antibiotic exposure to operator

Question 10

Construction of HEPA filters

Answer 10

Remove particles and direct airflow (unidirectional)

Need a large surface area = easier to push air through
Aluminium foil separator
Rated by efficiency to remove 99.97% of 0.3micrograms particles

Question 11

Mechanisms of particle removal

Answer 11

Diffusion = small particles
Impaction = large particles
Interception = medium
Sieving

Question 12

Filter efficiency factors

Answer 12

Particle density
Velocity and mean fee path of particle
Thickness of filter medium
Velocity, pressure and temperature of transporting gas
Sizing and distribution of fibres within the filter medium

Question 13

What is the design of cleanrooms for pharmaceutical industry?

Answer 13

Cleanroom suite needed
Various grades so need to accommodate different parts of the manufacturing process

Room for changing
Mixing
Filling room
Checking room

Aseptic and terminally sterilised products have different room classification requirements

Question 14

Design objective of cleanroom

Answer 14

Removal of particulates

Protect operators = can you get away with just a laminar flow unit?
- Keeping hazardous material away from operators

Optimum working conditions for operator and product

Effective monitoring of conditions

Control movement of operators

Can’t have parenteral and cytotoxic manufacture in same room

Ensure no wash over that may contaminate the product